Neurostimulation systems and methods for affecting cardiac contractility

ABSTRACT

A method of detecting catheter movement includes positioning a first sensor in a first body cavity, monitoring a first parameter profile of the first body cavity, positioning a second sensor in a second body cavity, monitoring a second parameter profile of the second body cavity, the second parameter profile different than the first parameter profile at a first time, and, when the second parameter profile is the same as the first parameter profile at a second time after the first time, taking a catheter movement action.

INCORPORATION BY REFERENCE

This application is a continuation of PCT Patent App. No.PCT/US2018/050522, filed on Sep. 11, 2018, which claims priority benefitof U.S. Provisional Patent Application No. 62/676,188, filed on May 24,2018, U.S. Provisional Patent Application No. 62/623,648, filed on Jan.30, 2018, and U.S. Provisional Patent Application No. 62/558,169, filedon Sep. 13, 2017, each of which is incorporated herein by reference inits entirety.

BACKGROUND Field

The present disclosure relates generally to methods and systems fordetecting catheter movement, selecting electrodes, calibration, ECGcompatibility, facilitating modulation (e.g., electricalneuromodulation), and/or manufacturing systems or devices therefor, Forexample, methods and systems for facilitating therapeutic andcalibration electrical neuromodulation of one or more nerves in andaround the heart are provided.

Description of the Related Art

Acute heart failure is a cardiac condition in which a problem with thestructure or function of the heart impairs its ability to supplysufficient blood flow to meet the body's needs. The condition impairsquality of life and is a leading cause of hospitalizations and mortalityin the western world. Treating acute heart failure is typically aimed atremoval of precipitating causes, prevention of deterioration in cardiacfunction, and control of the patient's congestive state.

SUMMARY

Treatments for acute heart failure include the use of inotropic agents,such as dopamine and dobutamine. These agents, however, have bothchronotropic and inotropic effects and characteristically increase heartcontractility at the expense of significant increases in oxygenconsumption secondary to elevations in heart rate. As a result, althoughthese inotropic agents increase myocardial contractility and improvehemodynamics, clinical trials have consistently demonstrated excessmortality caused by cardiac arrhythmias and increase in myocardiumconsumption.

As such, there is a need for selectively and locally treating acuteheart failure and otherwise achieving hemodynamic control withoutcausing unwanted systemic effects. Accordingly, in some examples, noinotropics are used. In other examples, reduced dosages of inotropicsmay be used because, for example, synergistic effects are providedthrough various examples herein. By reducing the dosages, the sideeffects can also be significantly reduced.

Several examples of the present disclosure provide for methods of tissuemodulation, such as neuromodulation, for cardiac and other disorders.For example, some examples provide methods and devices forneuromodulation of one or more nerves in and around a heart of apatient. Several methods of the present disclosure, for example, may beuseful in electrical neuromodulation of patients with cardiac disease,such as patients with acute or chronic cardiac disease. Several methodsof the present disclosure encompass, for example, neuromodulation of oneor more target sites of the autonomic nervous system of the heart. Insome examples, sensed non-electrical heart activity properties are usedin making adjustments to one or more properties of the electricalneuromodulation delivered to the patient. Non-limiting examples ofmedical conditions that can be treated according to the presentdisclosure include cardiovascular medical conditions.

As discussed herein, the configuration of the catheter and electrodesystems of the present disclosure may advantageously allow for a portionof the catheter to be positioned within the vasculature of the patientin the main pulmonary artery and/or one or both of the pulmonaryarteries (the right pulmonary artery and the left pulmonary artery).Once positioned, the catheter and electrode systems of the presentdisclosure can provide electrical stimulation energy (e.g., electricalcurrent or electrical pulses) to stimulate the autonomic nerve fiberssurrounding the main pulmonary artery and/or one or both of thepulmonary arteries in an effort to provide adjuvant cardiac therapy tothe patient.

The catheter can include an elongate body having a first end and asecond end. The elongate body can include an elongate radial axis thatextends through the first end and the second end of the elongate body,and a first plane extends through the elongate radial axis. At least twoelongate stimulation members may extend from the elongate body, whereeach of the at least two elongate stimulation members curves into afirst volume defined at least in part by the first plane. In oneexample, at least one electrode is on each of the at least two elongatestimulation members, where the at least one electrode form an electrodearray in the first volume. Conductive elements may extend through and/oralong each of the elongate stimulation members, where the conductiveelements conduct electrical current to combinations of two or more ofthe electrodes in the electrode array.

In one example, the at least two elongate stimulation members can curveonly in the first volume defined at least in part by the first plane,and a second volume defined at least in part by the first plane andbeing opposite the first volume contains no electrodes. A second planecan perpendicularly intersect the first plane along the elongate radialaxis of the elongate body to divide the first volume into a firstquadrant volume and a second quadrant volume. The at least two elongatestimulation members can include a first elongate stimulation member anda second elongate stimulation member, where the first elongatestimulation member curves into the first quadrant volume and the secondelongate stimulation member curves into the second quadrant volume.

Each of the at least two elongate stimulation members can include astimulation member elongate body and a wire extending longitudinallythrough the elongate body and the stimulation member elongate body,where pressure applied by the wire against the stimulation memberelongate body at or near its distal end causes the wire to deflect,thereby imparting the curve into each of the at least two elongatestimulation members into the first volume defined at least in part bythe first plane. The catheter can also include an anchor member thatextends from the elongate body into a second volume defined at least inpart by the first plane and opposite the first volume, where the anchormember does not include an electrode.

In an additional example, the catheter can also include a structureextending between at least two of the least two elongate stimulationmembers. An additional electrode can be positioned on the structure, theadditional electrode having a conductive element extending from theadditional electrode through one of the elongate stimulation members,where the conductive element conducts electrical current to combinationsof the additional electrode and at least one of the at least oneelectrode on each of the at least two elongate stimulation members. Anexample of such a structure is a mesh structure.

The catheter can also include a positioning gauge that includes anelongate gauge body with a first end and a bumper end distal to thefirst end. The elongate body of the catheter can include a first lumenthat extends from the first end through the second end of the elongatebody. The bumper end can have a shape with a surface area no less than asurface area of the distal end of the elongate body takenperpendicularly to the elongate radial axis, and the elongate gauge bodycan extend through the first lumen of the elongate body to position thebumper end beyond the second end of the elongate body. In one example,the first end of the positioning gauge extends from the first end of theelongate body, the elongate gauge body having a marking that indicates alength between the second end of the elongate body and the bumper end ofthe positioning gauge.

The present disclosure also includes a catheter system that includes acatheter and a pulmonary artery catheter having a lumen, where thecatheter extends through the lumen of the pulmonary artery catheter. Thepulmonary artery catheter can include an elongate catheter body with afirst end, a second end, a peripheral surface and an interior surface,opposite the peripheral surface, that defines the lumen extendingbetween the first end and the second end of the elongate catheter body.An inflatable balloon can be positioned on the peripheral surface of theelongate catheter body, the inflatable balloon having a balloon wallwith an interior surface that, along with a portion of the peripheralsurface of the elongate catheter body, defines a fluid tight volume. Aninflation lumen extends through the elongate catheter body, theinflation lumen having a first opening into the fluid tight volume ofthe inflatable balloon and a second opening proximal to the firstopening to allow for a fluid to move in and out of the fluid tightvolume to inflate and deflate the balloon.

The present disclosure also provides for a catheter that includes anelongate catheter body having a first end, a second end, a peripheralsurface and an interior surface defining an inflation lumen that extendsat least partially between the first end and the second end of theelongate catheter body; an inflatable balloon on the peripheral surfaceof the elongate catheter body, the inflatable balloon having a balloonwall with an interior surface that along with a portion of theperipheral surface of the elongate catheter body defines a fluid tightvolume, where the inflation lumen has a first opening into the fluidtight volume of the inflatable balloon and a second opening proximal tothe first opening to allow for a fluid to move in the volume to inflateand deflate the balloon; a plurality of electrodes positioned along theperipheral surface of the elongate catheter body, the plurality ofelectrodes located between the inflatable balloon and the first end ofthe elongate catheter body; conductive elements extending through theelongate catheter body, where the conductive elements conduct electricalcurrent to combinations of two or more of the at least one electrode ofthe plurality of electrodes; and a first anchor extending laterally fromthe peripheral surface of the elongate body, the first anchor havingstruts forming an open framework with a peripheral surface having alargest outer dimension greater than a largest outer dimension of theinflatable balloon.

In one example, the first anchor is positioned between the inflatableballoon and the plurality of electrodes positioned along the peripheralsurface of the elongate catheter body. A portion of the elongatecatheter body that includes the plurality of electrodes can curve in apredefined radial direction when placed under longitudinal compression.In another example, the first anchor is positioned between the pluralityof electrodes positioned along the peripheral surface of the elongatecatheter body and the first end of the elongate catheter body.

The elongate catheter body can also include a second interior surfacedefining a shaping lumen that extends from the first end towards thesecond end. A shaping wire having a first end and a second end can passthrough the shaping lumen with the first end of the shaping wireproximal to the first end of the elongate catheter body and the secondend of the shaping wire joined to the elongate catheter body so that theshaping wire imparts a curve into a portion of the elongate catheterbody having the plurality of electrodes when tension is applied to theshaping wire.

An example of the catheter can also include an elongate catheter bodyhaving a first end, a second end, a peripheral surface and an interiorsurface defining an inflation lumen that extends at least partiallybetween the first end and the second end of the elongate catheter body;an inflatable balloon on the peripheral surface of the elongate catheterbody, the inflatable balloon having a balloon wall with an interiorsurface that along with a portion of the peripheral surface of theelongate catheter body defines a fluid tight volume, where the inflationlumen has a first opening into the fluid tight volume of the inflatableballoon and a second opening proximal to the first opening to allow fora fluid to move in the volume to inflate and deflate the balloon; afirst anchor extending laterally from the peripheral surface of theelongate catheter body the first anchor having struts forming an openframework with a peripheral surface having a diameter larger than adiameter of the inflatable balloon; an electrode catheter having anelectrode elongate body and a plurality of electrodes positioned along aperipheral surface of the electrode elongate body; conductive elementsextending through the electrode elongate body of the electrode catheter,where the conductive elements conduct electrical current to combinationstwo or more of the at least one electrode of the plurality ofelectrodes; and an attachment ring joined to the electrode catheter andpositioned around the peripheral surface of the elongate catheter bodyproximal to both the first anchor and the inflatable balloon.

A catheter system of the present disclosure can also include an elongatecatheter body having a first end, a second end, a peripheral surface andan interior surface defining an inflation lumen that extends at leastpartially between the first end and the second end of the elongatecatheter body, where the elongate catheter body includes an elongateradial axis that extends through the first end and the second end of theelongate body, and where a first plane extends through the elongateradial axis; an inflatable balloon on the peripheral surface of theelongate catheter body, the inflatable balloon having a balloon wallwith an interior surface that along with a portion of the peripheralsurface of the elongate catheter body defines a fluid tight volume,where the inflation lumen has a first opening into the fluid tightvolume of the inflatable balloon and a second opening proximal to thefirst opening to allow for a fluid to move in the volume to inflate anddeflate the balloon; an electrode cage having two or more ribs thatextend radially away from the peripheral surface of the elongatecatheter body towards the inflatable balloon, where the two or more ofthe ribs of the electrode cage curve into a first volume defined atleast in part by the first plane; one or more electrodes on each of theribs of the electrode cage, where the one or more electrodes on each ofthe rib form an electrode array in the first volume; conductive elementsextending through the two or more of the ribs of the electrode cage andthe elongate catheter body, where the conductive elements conductelectrical current to combinations of the one or more electrodes in theelectrode array; and an anchoring cage having two or more of the ribsthat extend radially away from the peripheral surface of the elongatecatheter body towards the inflatable balloon, where the two or more ofthe ribs of the anchoring cage curve into a second volume defined atleast in part by the first plane and being opposite the first volume,where the two or more of the rib of the anchoring cage do not include anelectrode.

In one example, a catheter includes an elongate body having a first endand a second end. The elongate body includes a longitudinal center axisthat extends between the first end and the second end. The elongate bodyfurther includes three or more surfaces that define a convex polygonalcross-sectional shape taken perpendicularly to the longitudinal centeraxis. The catheter further includes one or more, but preferably two ormore, electrodes on one surface of the three or more surfaces of theelongate body, where conductive elements extend through the elongatebody. The conductive elements can conduct electrical current tocombinations of the one or more electrodes or in the instance of asingle electrode a second electrode is provided elsewhere in the systemfor flow of current. By way of example, the surfaces defining the convexpolygonal cross-sectional shape of the elongate body can be a rectangle.Other shapes are possible. In one example, the one or two or moreelectrodes are only on the one surface of the three or more surfaces ofthe elongate body. The one or more electrodes can have an exposed facethat is co-planar with the one surface of the three or more surfaces ofthe elongate body. The one surface of the three or more surfaces of theelongate body can further include anchor structures that extend abovethe one surface. In addition to the surfaces defining the convexpolygonal cross-sectional shape, the elongate body of the catheter canalso have a portion with a circular cross-section shape takenperpendicularly to the longitudinal center axis. The catheter of thisexample can also include an inflatable balloon on a peripheral surfaceof the elongate body. The inflatable balloon includes a balloon wallwith an interior surface that along with a portion of the peripheralsurface of the elongate body defines a fluid tight volume. An inflationlumen extends through the elongate body, the inflation lumen having afirst opening into the fluid tight volume of the inflatable balloon anda second opening proximal to the first opening to allow for a fluid tomove in the fluid tight volume to inflate and deflate the balloon.

In another example, a catheter includes an elongate body having aperipheral surface and a longitudinal center axis extending between afirst end and a second end. The elongate body of this example has anoffset region defined by a series of predefined curves along thelongitudinal center axis. The predefined curves include a first portionhaving a first curve and a second curve in the longitudinal center axis,a second portion following the first portion, where the second portionhas a zero curvature (e.g., a straight portion), and a third portionfollowing the second portion, the third portion having a third curve anda fourth curve. An inflatable balloon is positioned on the peripheralsurface of the elongate body, the inflatable balloon having a balloonwall with an interior surface that along with a portion of theperipheral surface of the elongate body defines a fluid tight volume. Aninflation lumen extends through the elongate body, the inflation lumenhaving a first opening into the fluid tight volume of the inflatableballoon and a second opening proximal to the first opening to allow fora fluid to move in the fluid tight volume to inflate and deflate theballoon. One or more electrodes are positioned on the elongate bodyalong the second portion of the offset region of the elongate body.Conductive elements extend through the elongate body, where theconductive elements conduct electrical current to combinations of theone or more electrodes. The portions of the elongate body of thisexample of a catheter can have a variety of shapes. For example, thesecond portion of the elongate body can form a portion of a helix. Theelongate body can also have three or more surfaces defining a convexpolygonal cross-sectional shape taken perpendicularly to thelongitudinal center axis, where the one or more electrodes are on onesurface of the three or more surfaces of the elongate body. For thisexample, the convex polygonal cross-sectional shape can be a rectangle.The one or more electrodes are only on the one surface of the three ormore surfaces of the elongate body. The one or more electrodes can havean exposed face that is co-planar with the one surface of the three ormore surfaces of the elongate body.

In another example, a catheter includes an elongate body with aperipheral surface and a longitudinal center axis extending between afirst end and a second end. The elongate body includes a surfacedefining a deflection lumen, where the deflection lumen includes a firstopening and a second opening in the elongate body. An inflatable balloonis located on the peripheral surface of the elongate body, theinflatable balloon having a balloon wall with an interior surface thatalong with a portion of the peripheral surface of the elongate bodydefines a fluid tight volume. An inflation lumen extends through theelongate body, the inflation lumen having a first opening into the fluidtight volume of the inflatable balloon and a second opening proximal tothe first opening to allow for a fluid to move in the fluid tight volumeto inflate and deflate the balloon. One or more electrodes are locatedon the elongate body, where the second opening of the deflection lumenis opposite the one or more electrodes on the elongate body. Conductiveelements extend through the elongate body, where the conductive elementsconduct electrical current to combinations of the one or moreelectrodes. The catheter also includes an elongate deflection member,where the elongate deflection member extends through the second openingof the deflection lumen in a direction opposite the one or moreelectrodes on one surface of the elongate body.

In another example, a catheter includes an elongate body having aperipheral surface and a longitudinal center axis extending between afirst end and a second end. The elongate body includes a surfacedefining an electrode lumen, where the electrode lumen includes a firstopening in the elongate body. The catheter further includes aninflatable balloon on the peripheral surface of the elongate body, theinflatable balloon having a balloon wall with an interior surface thatalong with a portion of the peripheral surface of the elongate bodydefines a fluid tight volume. An inflation lumen extends through theelongate body, the inflation lumen having a first opening into the fluidtight volume of the inflatable balloon and a second opening proximal tothe first opening to allow for a fluid to move in the fluid tight volumeto inflate and deflate the balloon. The catheter further includes anelongate electrode member, where the elongate electrode member extendsthrough the first opening of the electrode lumen of the elongate body,where the electrode member includes one or more electrodes andconductive elements extending through the electrode lumen, where theconductive elements conduct electrical current to combinations of theone or more electrodes. The elongate electrode member can form a loopthat extends away from the peripheral surface of the elongate body. Theelongate electrode member forming the loop can be in a plane that isco-linear with the longitudinal center axis of the elongate body.Alternatively, the elongate electrode member forming the loop is in aplane that is perpendicular to the longitudinal center axis of theelongate body.

According to some methods of the present disclosure and as will bediscussed more fully herein, a catheter having an electrode array isinserted into the pulmonary trunk and positioned at a location such thatthe electrode array is positioned with its electrodes in contact withthe posterior surface, the superior surface and/or the inferior surfaceof the right pulmonary artery. From this location, electrical currentcan be delivered to or from the electrode array to selectively modulatethe autonomic nervous system of the heart. For example, electricalcurrent can be delivered to or from the electrode array to selectivelymodulate the autonomic cardiopulmonary nerves of the autonomic nervoussystem, which can modulate heart contractility more than heart rate.Preferably, the electrode array is positioned at a site along theposterior wall and/or superior wall of the right pulmonary artery suchthat the electrical current delivered to or from the electrode arrayresults in the greatest effect on heart contractility and the leasteffect on heart rate and/or oxygen consumption compared to electricalcurrent delivered at other sites in the right pulmonary artery and/orleft pulmonary artery. In certain examples, the effect on heartcontractility is to increase heart contractility.

As used herein, the electrical current delivered to or from theelectrode array can be in the form of a time variant electrical current.Preferably such a time variant electrical current can be in the form ofone or more of a pulse of electrical current (e.g., at least one pulseof electrical current), one or more of waveform, such as a continuouswave of electrical current, or a combination thereof.

As discussed herein, the present disclosure provides for a method fortreating a patient having a heart with a pulmonary trunk. Portions ofthe pulmonary trunk can be defined with a right lateral plane thatpasses along a right luminal surface of the pulmonary trunk, a leftlateral plane parallel with the right lateral plane, where the leftlateral plane passes along a left luminal surface of the pulmonarytrunk. The right lateral plane and the left lateral plane extend in adirection that generally aligns with the posterior and anteriordirections of a subject's (e.g., patient's) body. A branch point ispositioned between the right lateral plane and the left lateral plane,where the branch point helps to define the beginning of a left pulmonaryartery and a right pulmonary artery of the heart. The method furtherincludes moving a catheter having an electrode array through thepulmonary trunk towards the branch point, where the electrode arrayincludes one or more, preferably two or more, electrodes. The electrodearray is positioned in the right pulmonary artery to the right of theleft lateral plane, where the one or more electrodes contacts aposterior surface, a superior surface and/or an inferior surface of theright pulmonary artery to the right of the left lateral plane. In anadditional example, the electrode array can be positioned in the rightpulmonary artery to the right of the right lateral plane, where the oneor more electrodes contacts the posterior surface, the superior surfaceand/or the inferior surface of the right pulmonary artery to the rightof the right lateral plane. This example of a method further includescontacting the one or more electrodes on the posterior surface, thesuperior surface and/or the inferior surface of the right pulmonaryartery at a position superior to (e.g., situated above) the branchpoint. The at least a portion of the catheter can also be positioned incontact with a portion of the surface defining the branch point. In thisexample, the portion of the catheter can be provided with a shape thatprovides an increase in surface area that can help to hold the portionof the catheter against the branch point.

In an additional example, the pulmonary trunk has a diameter takenacross a plane perpendicular to both the left lateral plane and theright lateral plane, where the electrode array is positioned in theright pulmonary artery to extend from a point to the right of the leftlateral plane to a point about three times the diameter of the pulmonarytrunk to the right of the branch point. The right pulmonary artery canalso include a branch point that divides the right pulmonary artery intoat least two additional arteries that are distal to the branch pointhelping to define the beginning of the left pulmonary artery and theright pulmonary artery. The electrode array can be positioned in theright pulmonary artery between the branch point helping to define thebeginning of the left pulmonary artery and the right pulmonary arteryand the branch point that divides the right pulmonary artery into atleast two additional arteries. Once in position, electrical current canbe provided from or to the one or more electrodes of the electrodearray. A value of a cardiac parameter of the patient can be measured inresponse to the electrical current from or to the one or more electrodesof the electrode array. From the value of the cardiac parameter, changescan be made to which of the electrodes are used to provide theelectrical current in response to the value of the cardiac parameter.Changes can also be made to the nature of the electrical currentprovided in response to the value of the cardiac parameter. Such changesinclude, but are not limited to, changes in voltage, amperage, waveform,frequency and pulse width, by way of example. In addition, theelectrodes of the one or more electrodes on the posterior surface, thesuperior surface and/or the inferior surface of the right pulmonaryartery can be moved in response to the values of the cardiac parameter.The electrical current provided to or from the one or more electrodes ofthe electrode array can be provided as at least one pulse of electricalcurrent to or from the one or more electrodes of the electrode array.Examples of such a cardiac parameter include, but are not limited to,measuring a pressure parameter, an acoustic parameter, an accelerationparameter and/or an electrical parameter (e.g., ECG) of the heart of thepatient as the cardiac parameter.

Several methods of the present disclosure allow for electricalneuromodulation of the heart of the patient, for example includingdelivering one or more electrical pulses through a catheter positionedin a pulmonary artery of the heart of the patient, sensing from at leasta first sensor positioned at a first location within the vasculature ofthe heart one or more heart activity properties (e.g., a non-electricalheart activity property) in response to the one or more electricalpulses, and adjusting a property of the one or more electrical pulsesdelivered through the catheter positioned in the pulmonary artery of theheart in response to the one or more heart activity properties. Themethods may provide adjuvant cardiac therapy to the patient.

Sensing from at least the first sensor positioned at the first locationcan include sensing one or more of a pressure property, an accelerationproperty, an acoustic property, a temperature, and a blood chemistryproperty from within the vasculature of the heart. Among otherlocations, the first sensor can be positioned in one of a left pulmonaryartery, a right pulmonary artery, a pulmonary artery branch vessel, or apulmonary trunk of the heart. The one or more electrical pulses canoptionally be delivered through the catheter positioned in one of theleft pulmonary artery, the right pulmonary artery, or pulmonary trunk ofthe heart that does not contain the first sensor. The first sensor canalso be positioned in a pulmonary trunk of the heart.

Other locations for the first sensor can include in the right ventricleof the heart and in the right atrium of the heart. When positioned inthe right atrium of the heart, the first sensor can optionally bepositioned on the septal wall of the right atrium of the heart. Thefirst sensor could also be positioned on the septal wall of the rightventricle. The right ventricle and the left ventricle share a septalwall, so a sensor in the right ventricle or on the septal wall of theright ventricle may be preferable for detecting properties indicative ofleft ventricle contractility or cardiac output. Additional locations forpositioning the first sensor include in a superior vena cava of theheart, the inferior vena cava of the heart, and in a coronary sinus ofthe heart. When positioned in the coronary sinus of the heart, the firstsensor can be used to sense at least one of a temperature or a bloodoxygen level.

In some examples, the first sensor may be positioned in the left atrium(e.g., by forming an aperture in the septal wall between the rightatrium and the left atrium, or by using a patent foramen ovale (PFO) oratrial septal defect (ASD)). A sensor in the left atrium may be usefulfor detecting properties indicative of the left ventricle. If the leftatrium has been accessed, in some examples, the sensor may be positionedin the left ventricle itself, which may provide the most directmeasurement of properties associated with the left ventricle. In someexamples, the sensor may be positioned downstream of the left ventricle,including the aorta, aortic branch arteries, etc. When the procedure iscomplete, any aperture that was created or existing may be closed usinga closure device such as Amplatzer, Helex, CardioSEAL, or others.

Some methods can include sensing one or more cardiac properties from askin surface of the patient, and adjusting the property of the one ormore electrical pulses delivered through the catheter positioned in thepulmonary artery of the heart in response to the one or more heartactivity properties (e.g., non-electrical properties) from the firstsensor positioned at a first location within the vasculature of theheart and/or the one or more cardiac properties from the skin surface ofthe patient. The one or more cardiac properties sensed from the skinsurface of the patient can include, for example, an electrocardiogramproperty.

Some methods can include sensing from at least a second sensorpositioned at a second location within the vasculature of the heart oneor more heart activity properties (e.g., non-electrical heart activityproperties) in response to the one or more electrical pulses, andadjusting the property of the one or more electrical pulses deliveredthrough the catheter positioned in the pulmonary artery of the heart inresponse to the one or more heart activity properties from the firstsensor and/or the one or more heart activity properties from the secondsensor.

Adjusting the property of the one or more electrical pulses can includea variety of responses. For example, adjusting the property of the oneor more electrical pulses can include changing which of an electrode orplurality of electrodes on the catheter is used to deliver the one ormore electrical pulses. For another example, adjusting the property ofthe one or more electrical pulses can include moving the catheter toreposition one or more electrodes of the catheter in the pulmonaryartery of the heart. For yet another example, adjusting the property ofthe one or more electrical pulses can include changing at least one ofan electrode polarity, a pulsing mode, a pulse width, an amplitude, afrequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, and/or awaveform of the one or more electrical pulses.

A hierarchy of electrode configurations can be assigned from which todeliver the one or more electrical pulses. The one or more electricalpulses can be delivered based on the hierarchy of electrodeconfigurations, where the one or more heart activity properties sensedin response to the one or more electrical pulses can be analyzed and anelectrode configuration can be selected to use for delivering the one ormore electrical pulses through the catheter positioned in the pulmonaryartery of a heart of a patient based on the analysis. A hierarchy can beassigned to each property of the one or more electrical pulses deliveredthrough the catheter positioned in the pulmonary artery of the heart,where the one or more electrical pulses are delivered based on thehierarchy of each property. The one or more non-electrical heartactivity properties sensed in response to the one or more electricalpulses are analyzed and an electrode configuration can be selected to beused for delivering the one or more electrical pulses through thecatheter positioned in the pulmonary artery of a heart of a patientbased on the analysis. Analyzing the one or more heart activityproperties can include analyzing a predetermined number of the one ormore heart activity properties.

In some examples, a method of detecting catheter movement comprisespositioning a first sensor in a first body cavity, monitoring a firstparameter profile of the first body cavity, positioning a second sensorin a second body cavity, monitoring a second parameter profile of thesecond body cavity, the second parameter profile different than thefirst parameter profile at a first time, and, when the second parameterprofile is the same as the first parameter profile at a second timeafter the first time, taking a catheter movement action. In someexamples, a method of detecting catheter movement is non-therapeutic andneed not be performed by a physician.

The first sensor may comprise a first pressure sensor. The first sensormay comprise a first pressure sensor. The first pressure sensor maycomprise a MEMS sensor. The first parameter profile may comprise apressure range. The second sensor may comprise a second pressure sensor.The second pressure sensor may comprise a MEMS sensor. The secondparameter profile may comprise a pressure range. The first body cavitymay comprise a pulmonary artery and the second body cavity may comprisea right ventricle. The first body cavity may comprise a right ventricleand the second body cavity may comprise a right atrium. The first bodycavity may comprise a right atrium and the second body cavity maycomprise a vena cava. The catheter movement action may comprise soundingan alarm. The catheter movement action may comprise stoppingneurostimulation. The catheter movement action may comprise collapsingan expandable element. The catheter movement action may comprise sendinga wireless message.

In some examples, a system for detecting movement of a cathetercomprises a first sensor configured to be positioned in a first bodycavity and to monitor a first parameter profile of the first body cavityand a second sensor configured to be positioned in a second body cavityand to monitor a second parameter profile of the second body cavity. Thesecond parameter profile is different than the first parameter profileat a first time. The second parameter profile being the same as thefirst parameter profile at a second time after the first time indicatesmovement of the catheter.

The first sensor may comprise a first pressure sensor. The firstpressure sensor may comprise a MEMS sensor. The first parameter profilemay comprise a pressure range. The second sensor may comprise a secondpressure sensor. The second pressure sensor may comprise a MEMS sensor.The second parameter profile may comprise a pressure range. The systemmay further comprise the catheter. The catheter may comprise the firstsensor and the second sensor. The second sensor may be proximal to thefirst sensor.

In some examples, a method of detecting catheter movement comprisespositioning a sensor in a right ventricle and using the sensor tomonitor a parameter profile of the right ventricle for a change greaterthan a threshold value. In some examples, a method of detecting cathetermovement is non-therapeutic and need not be performed by a physician.

The threshold value may be indicative of movement of the sensor againsta tricuspid valve. The threshold value may be indicative of movement ofthe sensor proximal to a tricuspid valve. The parameter may comprisepressure. The sensor may comprise a MEMS sensor. A catheter may comprisethe sensor. Positioning the sensor in the right ventricle may compriseproviding slack to the catheter. Upon proximal retraction of thecatheter, the catheter may be made taut and the sensor may be movedtowards an annulus of a tricuspid valve. The method may further comprisedetecting the change greater than the threshold value and taking acatheter movement action. The catheter movement action may comprisesounding an alarm (e.g., sending a wireless message). The cathetermovement action may comprise stopping neurostimulation. The cathetermovement action may comprise collapsing an expandable element. Thecatheter movement action may comprise sending a wireless message.

In some examples, a system for detecting movement of a cathetercomprises a sensor configured to be positioned in a right ventricle andto monitor a parameter profile of the right ventricle. A change in theparameter profile greater than a threshold value indicates movement ofthe catheter.

The threshold value is indicative of movement of the sensor against atricuspid valve. The threshold value is indicative of movement of thesensor proximal to a tricuspid valve. The parameter may comprisepressure. The sensor may comprise a MEMS sensor. The system may furthercomprise the catheter. The catheter may comprise the sensor.

In some examples, a method of facilitating therapeutic neuromodulationof a heart of a patient comprises positioning an electrode in apulmonary artery of a heart and positioning a sensor in a rightventricle of the heart. The method further comprises delivering, via astimulation system, a first series of electrical signals to theelectrode. The first series comprises a first plurality of electricalsignals. Each of the first plurality of electrical signals comprises aplurality of parameters. Each of the first plurality of electricalsignals of the first series only differs from one another by a magnitudeof a first parameter of the plurality of parameters. The method furthercomprises, after delivering the first series of electrical signals tothe electrode, delivering, via the stimulation system, a second seriesof electrical signals to the electrode. The second series comprises asecond plurality of electrical signals. Each of the second plurality ofelectrical signals comprises the plurality of parameters. Each of thesecond plurality of electrical signals of the second series only differsfrom one another by a magnitude of a second parameter of the pluralityof parameters. The second parameter is different than the firstparameter. The method further comprises determining, via the sensor,sensor data indicative of one or more non-electrical heart activityproperties in response to delivering the first series of electricalsignals and the second series of electrical signals, and delivering atherapeutic neuromodulation signal to the pulmonary artery usingselected electrical parameters. The selected electrical parameterscomprise a selected magnitude of the first parameter and a selectedmagnitude of the second parameter. The selected magnitudes of the firstand second parameters are based at least partially on the sensor data.The therapeutic neuromodulation signal increases heart contractilitymore than heart rate.

The method may further comprise delivering, via the stimulation system,a third series of electrical signals to the electrode. The third seriescomprises a third plurality of electrical signals. Each of the thirdplurality of electrical signals comprises the plurality of parameters.Each of the third plurality of electrical signals of the third seriesonly differs from one another by a magnitude of a third parameter of theplurality of parameters. The third parameter is different than the firstparameter and the second parameter. The method may further comprisedetermining, via the sensor, sensor data indicative of the one or morenon-electrical heart activity properties in response to delivering thethird series of electrical signals. The selected electrical parametersmay comprise a selected magnitude of the third parameter. The selectedmagnitude of the third parameter is based at least partially on thesensor data.

The method may further comprise determining a desired hierarchy betweenthe first series and the second series. The pulmonary artery maycomprise a right pulmonary artery. The one or more non-electrical heartactivity properties may comprise at least one of a pressure property, anacceleration property, an acoustic property, a temperature, and a bloodchemistry property. Determining the sensor data may comprisedetermining, via a second sensor on a skin surface, sensor dataindicative of an electrocardiogram property in response to deliveringthe first series of electrical signals and the second series ofelectrical signals.

The first parameter may be one of the following: a polarity, a pulsingmode, a pulse width, an amplitude, a frequency, a phase, a voltage, acurrent, a duration, an inter-pulse interval, a duty cycle, a dwelltime, a sequence, a wavelength, a waveform, or an electrode combination,and, optionally, the second parameter may be a different one of thefollowing: a polarity, a pulsing mode, a pulse width, an amplitude, afrequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, awaveform, or an electrode combination. The second parameter may be oneof the following: a polarity, a pulsing mode, a pulse width, anamplitude, a frequency, a phase, a voltage, a current, a duration, aninter-pulse interval, a duty cycle, a dwell time, a sequence, awavelength, a waveform, or an electrode combination. The first parametermay comprise current and the second parameter may comprise a parameterrelating to timing (e.g., one of frequency and duty cycle).

In some examples, a method of facilitating therapeutic neuromodulationof a heart of a patient comprises positioning an electrode in apulmonary artery of a heart, positioning a sensor in a right ventricleof the heart, delivering, via a stimulation system, a first electricalsignal of a series of electrical signals to the electrode, and, afterdelivering the first electrical signal, delivering, via the stimulationsystem, a second electrical signal of the series of electrical signalsto the electrode. The second electrical signal differs from the firstelectrical signal by a magnitude of a first parameter of a plurality ofparameters. The method further comprises determining, via the sensor,sensor data indicative of one or more non-electrical heart activityproperties in response to the delivery of the series of electricalsignals, and delivering a therapeutic neuromodulation signal to thepulmonary artery using selected electrical parameters. The selectedelectrical parameters comprise a selected magnitude of the firstparameter. The selected magnitude of the first parameter is based atleast partially on the sensor data. The therapeutic neuromodulationsignal increases heart contractility more than heart rate.

The pulmonary artery may comprise a right pulmonary artery. Thepulmonary artery may comprise a left pulmonary artery. The pulmonaryartery may comprise a pulmonary trunk. The one or more non-electricalheart activity properties may comprise at least one of a pressureproperty, an acceleration property, an acoustic property, a temperature,and a blood chemistry property. Determining the sensor data may comprisedetermining, via a second sensor on a skin surface of the patient,sensor data indicative of an electrocardiogram property in response todelivering the series of electrical signals. The first parameter may beone of the following: a polarity, a pulsing mode, a pulse width, anamplitude, a frequency, a phase, a voltage, a current, a duration, aninter-pulse interval, a duty cycle, a dwell time, a sequence, awavelength, a waveform, or an electrode combination.

In some examples, a method of facilitating therapeutic neuromodulationof a heart of a patient comprises delivering a first series ofelectrical signals to an electrode in a first anatomical location, and,after delivering the first series of electrical signals to theelectrode, delivering a second series of electrical signals to theelectrode. The first series comprises a first plurality of electricalsignals. Each of the first plurality of electrical signals comprises aplurality of parameters. Each of the first plurality of electricalsignals of the first series only differs from one another by a magnitudeof a first parameter of the plurality of parameters. The second seriescomprises a second plurality of electrical signals. Each of the secondplurality of electrical signals comprises the plurality of parameters.Each of the second plurality of electrical signals of the second seriesonly differs from one another by a magnitude of a second parameter ofthe plurality of parameters. The second parameter is different than thefirst parameter. The method further comprises sensing, via a sensor in asecond anatomical location different than the first anatomical location,sensor data indicative of one or more non-electrical heart activityproperties in response to delivering the first series of electricalsignals and the second series of electrical signals, and providing atherapeutic neuromodulation signal to the first anatomical locationusing selected electrical parameters. The selected electrical parameterscomprise a selected magnitude of the first parameter and a selectedmagnitude of the second parameter. The selected magnitudes of the firstand second parameters are based at least partially on the sensor data.The therapeutic neuromodulation signal increases heart contractility.

The method may further comprise delivering a third series of electricalsignals to the electrode. The third series comprises a third pluralityof electrical signals. Each of the third plurality of electrical signalscomprises the plurality of parameters. Each of the third plurality ofelectrical signals of the third series only differs from one another bya magnitude of a third parameter of the plurality of parameters. Thethird parameter is different than the first parameter and the secondparameter. The method may further comprise sensing, via the sensor,sensor data indicative of the one or more non-electrical heart activityproperties in response to delivering the third series of electricalsignals. The selected electrical parameters may comprise a selectedmagnitude of the third parameter. The selected magnitude of the thirdparameter is based at least partially on the sensor data.

The method may further comprise determining a desired hierarchy betweenthe first series and the second series. The first anatomical locationmay comprise a right pulmonary artery. The pulmonary artery may comprisea left pulmonary artery. The pulmonary artery may comprise a pulmonarytrunk. The one or more non-electrical heart activity properties maycomprise at least one of a pressure property, an acceleration property,an acoustic property, a temperature, and a blood chemistry property.Sensing the sensor data may comprise determining, via a second sensor ona skin surface, sensor data indicative of an electrocardiogram propertyin response to delivering the first series of electrical signals and thesecond series of electrical signals.

The first parameter may one of the following: a polarity, a pulsingmode, a pulse width, an amplitude, a frequency, a phase, a voltage, acurrent, a duration, an inter-pulse interval, a duty cycle, a dwelltime, a sequence, a wavelength, a waveform, or an electrode combination,and, optionally, the second parameter may be a different one of thefollowing: a polarity, a pulsing mode, a pulse width, an amplitude, afrequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, awaveform, or an electrode combination. The second parameter may one ofthe following: a polarity, a pulsing mode, a pulse width, an amplitude,a frequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, awaveform, or an electrode combination. The first parameter may comprisecurrent and the second parameter may comprise a parameter related totiming (e.g., one of frequency and duty cycle).

In some examples, a method of facilitating therapeutic neuromodulationof a heart of a patient comprises delivering a first electrical signalof a series of electrical signals to an electrode in a first anatomicallocation, and, after delivering the first electrical signal, deliveringa second electrical signal of the series of electrical signals to theelectrode. The second electrical signal differs from the firstelectrical signal by a magnitude of a first parameter of a plurality ofparameters. The method further comprises sensing, via a sensor in asecond anatomical location different than the first anatomical location,sensor data indicative of one or more non-electrical heart activityproperties in response to the delivery of the series of electricalsignals, and providing a therapeutic neuromodulation signal to the firstanatomical location using selected electrical parameters. The selectedelectrical parameters comprise a selected magnitude of the firstparameter. The selected magnitude of the first parameter is based atleast partially on the sensor data. The therapeutic neuromodulationsignal increases heart contractility.

The first anatomical location may comprise a right pulmonary artery. Thefirst anatomical location may comprise a left pulmonary artery. Thefirst anatomical location may comprise a pulmonary trunk. The one ormore non-electrical heart activity properties may comprise at least oneof a pressure property, an acceleration property, an acoustic property,a temperature, and a blood chemistry property. Sensing the sensor datamay comprise sensing, via a second sensor on a skin surface of thepatient, sensor data indicative of an electrocardiogram property inresponse to delivering the series of electrical signals. The firstparameter may be one of the following: a polarity, a pulsing mode, apulse width, an amplitude, a frequency, a phase, a voltage, a current, aduration, an inter-pulse interval, a duty cycle, a dwell time, asequence, a wavelength, a waveform, or an electrode combination.

In some examples, a neuromodulation system for facilitating delivery ofelectric signals to a heart of a patient comprises a catheter and astimulation system. The catheter comprises a catheter body comprising aproximal end, a distal end, a lumen extending from the proximal endtowards the distal end, and an outer surface. The catheter furthercomprises an electrode on the outer surface. The electrode is configuredto deliver an electrical signal to a pulmonary artery of a patient. Thecatheter further comprises a sensor on the outer surface. The sensor isconfigured to sense a heart activity property from a location within invasculature of the patient. The stimulation system comprises a pulsegenerator configured to deliver a first series of electrical signals anda second series of electrical signals to the electrode. The first seriescomprises a first plurality of electrical signals. Each of the firstplurality of electrical signals comprises a plurality of parameters.Each of the first plurality of electrical signals of the first seriesonly differs from one another by a magnitude of a first parameter of theplurality of parameters. The second series comprises a second pluralityof electrical signals. Each of the second plurality of electricalsignals comprises the plurality of parameters. Each of the secondplurality of electrical signals of the second series only differs fromone another by a magnitude of a second parameter of the plurality ofparameters. The second parameter is different than the first parameter.The stimulation system further comprises a non-transitorycomputer-readable medium configured to store sensor data indicative ofone or more non-electrical heart activity properties in response todelivering the first series of electrical signals and the second seriesof electrical signals to the electrode, and a processor configured todetermine a selected magnitude of the first parameter and a selectedmagnitude of the second parameter based at least partially on the sensordata. The non-transitory computer readable medium is configured to storeselected electrical parameters including the selected magnitude of thefirst parameter and the selected magnitude of the second parameter. Thepulse generator is configured to deliver a therapeutic neuromodulationsignal to the electrode using selected electrical parameters.

In some examples, a neuromodulation system for facilitating delivery ofelectric signals to a heart of a patient comprises a catheter and astimulation system. The catheter comprises a catheter body comprising aproximal end, a distal end, a lumen extending from the proximal endtowards the distal end, and an outer surface. The catheter furthercomprises an electrode on the outer surface. The electrode is configuredto deliver an electrical signal to a pulmonary artery of a patient. Thecatheter further comprises a sensor on the outer surface. The sensor isconfigured to sense a heart activity property from a location within invasculature of the patient. The stimulation system comprises a pulsegenerator configured to deliver a series of electrical signals to theelectrode. The series comprises a first electrical signal and a secondelectrical signal. The second electrical signal differs from the firstelectrical signal by a magnitude of a first parameter of a plurality ofparameters. The stimulation system further comprises a non-transitorycomputer-readable medium configured to store sensor data indicative ofone or more non-electrical heart activity properties in response todelivering the series of electrical signals to the electrode, and aprocessor configured to determine a selected magnitude of the firstparameter based at least partially on the sensor data. Thenon-transitory computer readable medium is configured to store selectedelectrical parameters including the selected magnitude of the firstparameter. The pulse generator is configured to deliver a therapeuticneuromodulation signal to the electrode using selected electricalparameters.

In some examples, a neuromodulation system for facilitating delivery ofelectric signals to a heart of a patient comprises a catheter and ashaping wire. The catheter comprises a catheter body comprising aproximal end, a distal end, a lumen extending from the proximal endtowards the distal end, and an outer surface. The catheter furthercomprises an electrode on the outer surface. The electrode is configuredto deliver an electrical signal to a pulmonary artery of a patient. Theshaping wire is configured to be positioned in the lumen of the catheterbody. The shaping wire comprises a bent portion. When the shaping wireis inserted in the lumen of the catheter body, the catheter bodycomprises a curved portion corresponding to the bent portion of theshaping wire.

The heart activity property may comprise a non-electrical heartyactivity property. The non-electrical heart activity property maycomprise at least one of a pressure property, an acceleration property,an acoustic property, a temperature, and a blood chemistry property. Theelectrode may be configured to deliver the electrical signal to a rightpulmonary artery of the patient. The electrode may be configured to bepositioned in a different location than the sensor. The catheter systemmay comprise a plurality of electrodes including the electrode. Thelocation may be a pulmonary trunk, a right ventricle, a septal wall of aright ventricle, a right atrium, a septal wall of a right atrium, asuperior vena cava, a pulmonary branch artery vessel, an inferior venacava, or a coronary sinus. The neuromodulation system may furthercomprise a skin sensor configured to sense a cardiac property from askin surface of the patient. The heart activity property may comprise anon-electrical heart activity property and wherein the cardiac propertymay comprise an electrical cardiac property. The electrical cardiacproperty may comprise an electrocardiogram property.

In some examples, a method of neuromodulation of a heart of a patientcomprises positioning a catheter including an electrode in a pulmonaryartery of a heart, positioning a sensor in a location within vasculatureof the heart, delivering, via a stimulation system, a first set of oneor more electrical pulses to the electrode, the first set of one or moreelectrical pulses having a first pulse property, and, after deliveringthe first delivering set of one or more electrical pulses to theelectrode, delivering, via the stimulation system, a second set of oneor more electrical pulses to the electrode. The second set of one ormore electrical pulses has a second pulse property different than thefirst pulse property. The method further comprises deliveringtherapeutic electrical pulses to the pulmonary artery using an electrodeconfiguration selected by analyzing one or more heart activityproperties sensed, via the sensor, in response to the delivery of thefirst and second sets of electrical pulses. The electrode configurationcomprises the first pulse property or the second pulse property based atleast partially on the analysis. The therapeutic neuromodulation signalincreases heart contractility more than heart rate.

In some examples, a method of modulation (e.g., electricalneuromodulation) of a heart of a patient comprises delivering one ormore electrical pulses through a catheter positioned in a pulmonaryartery of the heart of the patient, sensing from at least a first sensorpositioned at a first location within a vasculature of the heart one ormore non-electrical heart activity properties in response to the one ormore electrical pulses, and adjusting a property of the one or moreelectrical pulses delivered through the catheter positioned in thepulmonary artery of the heart in response to the one or morenon-electrical heart activity properties.

In some examples, sensing from at least the first sensor positioned atthe first location may include sensing one or more of a pressureproperty, an acceleration property, an acoustic property, a temperature,and a blood chemistry property from within the vasculature of the heart.

In one example, a first sensor is placed in one of a left pulmonaryartery, a right pulmonary artery, or a pulmonary trunk of the heart. Oneor more electrical pulses are delivered through the catheter positionedin one of the left pulmonary artery, the right pulmonary artery, or thepulmonary trunk of the heart that does not contain the first sensor.

The first sensor may be positioned in the left pulmonary artery. Thefirst sensor may be positioned in the right pulmonary artery. The firstsensor may be positioned in other vessels in and around the heart,including, but not limited to, the pulmonary trunk, a pulmonary arterybranch vessel, right ventricle, a septal wall of the right ventricle, aright atrium, the septal wall of the right atrium, a superior vena cava,an inferior vena cava or a coronary sinus The first sensor (e.g., in thecoronary sinus) may sense at least one of a temperature or a bloodoxygen level.

In several examples, the method may include sensing one or more cardiacproperties from a skin surface of the patient and adjusting the propertyof the one or more electrical pulses delivered through the catheterpositioned in the pulmonary artery of the heart in response to the oneor more non-electrical heart activity properties and the one or morecardiac properties from the skin surface of the patient. The one or morecardiac properties sensed from the skin surface of the patient mayinclude an electrocardiogram property. The may include sensing from atleast a second sensor positioned at a second location within thevasculature of the heart one or more non-electrical heart activityproperties in response to the one or more electrical pulses andadjusting the property of the one or more electrical pulses deliveredthrough the catheter positioned in the pulmonary artery of the heart inresponse to the one or more non-electrical heart activity propertiesreceived by the first sensor and the second sensor. In several examples,adjusting the property of the one or more electrical pulses may includeone or more of the following (i) changing which electrode on thecatheter is used to deliver the one or more electrical pulses; (ii)moving the catheter to reposition electrodes of the catheter in thepulmonary artery of the heart; (iii) changing at least one of anelectrode polarity, a pulsing mode, a pulse width, an amplitude, afrequency, a phase, a voltage, a current, a duration, an inter-pulseinterval, a duty cycle, a dwell time, a sequence, a wavelength, awaveform, or an electrode combination of the one or more electricalpulses.

In several examples, the method may include assigning a hierarchy ofelectrode configurations from which to deliver the one or moreelectrical pulses, delivering the one or more electrical pulses based atleast partially on the hierarchy of electrode configurations, analyzingthe one or more non-electrical heart activity properties sensed inresponse to the one or more electrical pulses, and selecting anelectrode configuration to use for delivering the one or more electricalpulses through the catheter positioned in the pulmonary artery of aheart of a patient based at least partially on the analysis. The methodmay include assigning a hierarchy to each property of the one or moreelectrical pulses delivered through the catheter positioned in thepulmonary artery of the heart, delivering the one or more electricalpulses based at least partially on the hierarchy of each property,analyzing the one or more non-electrical heart activity propertiessensed in response to the one or more electrical pulses, and selectingan electrode configuration to use for delivering the one or moreelectrical pulses through the catheter positioned in the pulmonaryartery of a heart of a patient based at least partially on the analysis.Analyzing the one or more non-electrical heart activity properties mayinclude analyzing a predetermined number of the one or morenon-electrical heart activity properties.

In several examples, therapeutic neuromodulation is not provided.Instead, several examples are provided for the purposes of calibratingor optimizing a signal for, e.g., diagnosis or calibration purposes.

In some examples, a method of non-therapeutic calibration comprisespositioning an electrode in a pulmonary artery of a heart andpositioning a sensor in a right ventricle of the heart. The systemfurther comprises delivering, via a stimulation system, a first seriesof electrical signals to the electrode. The first series comprises afirst plurality of electrical signals. Each of the first plurality ofelectrical signals comprises a plurality of parameters. Each of thefirst plurality of electrical signals of the first series only differsfrom one another by a magnitude of a first parameter of the plurality ofparameters. The method further comprises, after delivering the firstseries of electrical signals to the electrode, delivering, via thestimulation system, a second series of electrical signals to theelectrode. The second series comprises a second plurality of electricalsignals. Each of the second plurality of electrical signals comprisesthe plurality of parameters. Each of the second plurality of electricalsignals of the second series only differs from one another by amagnitude of a second parameter of the plurality of parameters. Thesecond parameter is different than the first parameter. The methodfurther comprises determining, via the sensor, sensor data indicative ofone or more non-electrical heart activity properties in response todelivering the first series of electrical signals and the second seriesof electrical signals. The method further comprises determining atherapeutic neuromodulation signal to be delivered to the pulmonaryartery using selected electrical parameters. The selected electricalparameters comprise a selected magnitude of the first parameter and aselected magnitude of the second parameter. The selected magnitudes ofthe first and second parameters are based at least partially on thesensor data.

In some examples, a method of non-therapeutic calibration comprisesdelivering a first electrical signal of a series of electrical signalsto an electrode in a first anatomical location and, after delivering thefirst electrical signal, delivering a second electrical signal of theseries of electrical signals to the electrode. The second electricalsignal differs from the first electrical signal by a magnitude of afirst parameter of a plurality of parameters. The method furthercomprises sensing, via a sensor in a second anatomical locationdifferent than the first anatomical location, sensor data indicative ofone or more non-electrical heart activity properties in response to thedelivery of the series of electrical signals, and determining atherapeutic neuromodulation signal to be delivered to the firstanatomical location using selected electrical parameters. The selectedelectrical parameters comprise a selected magnitude of the firstparameter. The selected magnitude of the first parameter is based atleast partially on the sensor data.

In some examples, a device comprises or consists essentially of a firstpart and a second part. The first part comprises a first annular portionhaving a first diameter and a first plurality of splines extendingdistally from the first annular portion. The second part comprises asecond annular portion having a second diameter and a second pluralityof splines extending distally and radially outward from the secondannular portion. The second diameter is less than the first diameter.The second annular portion is telescopeable in the first annularportion. Each of the first plurality of splines is coupled to one splineof the second plurality of splines. Upon distal longitudinal advancementof the second part relative to the first part, the first part expandsfrom a collapsed state to an expanded state. The first plurality ofsplines is circumferentially spaced in the expanded state. Upon proximallongitudinal retraction of the second part relative to the first part,the first part collapses from the expanded state to the collapsed state.

A distal end of each of the first plurality of splines may be coupled toone spline of the second plurality of splines.

The distal end of each of the first plurality of splines may be coupledto one spline of the second plurality of splines proximal to a distalend of the one of the second plurality of splines. The distal ends ofthe second plurality of splines may comprise fixation elements. At leastsome of the first plurality of splines may comprise electrodes. Eachspline of the first plurality of splines may comprise a plurality ofelectrodes. The plurality of electrodes may at least partially formingan electrode matrix.

The device may further comprise a membrane coupled to the firstplurality of splines, the membrane comprising a plurality of electrodes,the plurality of electrodes at least partially forming an electrodematrix. A longitudinal length from a proximal end of a proximal-mostelectrode of the plurality of electrodes to a distal end of adistal-most electrode the plurality of electrodes may be between 20 mmand 40 mm. A diameter of the first plurality of splines in the expandedstate may be between 15 mm and 35 mm.

The device may further comprise a catheter coupled to the first annularportion and an inner member in a lumen of the catheter and coupled tothe second annular portion. The inner member may be movable relative tothe catheter to distally advance and proximally retract the second part.A proximal end of the first annular portion may be coupled in a distalend of a lumen of the catheter. A proximal end of the second annularportion may be coupled in a distal end of a lumen of the inner member.The inner member may be trackable over a guidewire.

The device may further comprise a gripper coupled to the inner member, aspring engaging the gripper, and a handle element coupled to the innermember. Upon distal advancement of the handle element, the spring may belongitudinally expanded, the inner member may be distally longitudinallyadvanced, the second part may be distally longitudinally advanced, andthe first part may expand from the collapsed state to the expandedstate. Upon proximal retraction of the handle element, the spring may belongitudinally compressed, the inner member may be proximallylongitudinally retracted, the second part may be proximallylongitudinally retracted, and the first part collapses from the expandedstate to the collapsed state. The spring may be configured to at leastpartially proximally retract the handle element.

The device may further comprise a locking mechanism configured tomaintain the handle element in a distally advanced state. The lockingelement may comprise a plurality of arms having an open proximal end.The handle element may be configured to extend through the open proximalend upon distal advancement. The locking element may comprise aplurality of arms having closed proximal end. The handle element may beconfigured to engage the closed proximal end upon distal advancement.The plurality of arms may comprise leaf springs. The leaf springs may beconfigured to at least partially proximally retract the handle element.

The first plurality of splines may be not self-expanding. The firstplurality of splines may be self-expanding. The first plurality ofsplines may comprise a non-tapered shape in the expanded state. Thefirst part may comprise a first cut hypotube. The first annular portionmay comprise a hypotube and the first plurality of splines may comprisea plurality of wires. The second part may comprise second a cuthypotube.

In some examples, a device comprises or consists essentially of aplurality of splines, a structure coupled to at least one spline of theplurality of splines, and an electrode coupled to the structure.

The device may comprise a plurality of electrodes coupled to thestructure. The plurality of electrodes may be the electrode. Theplurality of electrodes may at least partially form an electrode matrix.The electrode matrix may comprise a 3×4 matrix.

The structure may be coupled to at least two splines of the plurality ofsplines. The electrode may be circumferentially between two splines ofthe plurality of splines. The electrode may be circumferentially alignedwith a spline of the plurality of splines.

The device may further comprise a second electrode coupled to one of theplurality of splines. The structure may comprise a plurality of flexiblestrands connected to form a pattern of openings. The structure maycomprise a mesh. The structure may comprise a woven or knitted membrane.The structure may comprise shape memory material having an expandedshape when not confined. The structure may comprise insulative material.

In some examples, a device comprises or consists essentially of a firstsidewall, a second sidewall spaced from the first sidewall, and a thirdsidewall between the first sidewall and the second sidewall. The firstsidewall, the second sidewall, and the third sidewall at least partiallydefine a U-shaped trough. The device further comprises a plurality ofconductors in the trough and an electrode electrically connected to oneof the plurality of conductors.

The device may comprise a plurality of electrodes including theelectrode. The plurality of electrodes may at least partially form anelectrode matrix. Each of the plurality of electrodes may beelectrically connected to one of the plurality of conductors. Theelectrode may have a dome shape.

The device may further comprise insulative material between theplurality of conductors and the electrode. The device may furthercomprise insulative material between the plurality of conductors and thethird sidewall. The device may further comprise insulating materialextending at least above a bottom of the electrode. The insulatingmaterial may comprise a dome shape. The insulating material may comprisea flat upper surface. The insulating material may comprise a crownedsurface. The insulating material may cover a sharp edge of theelectrode.

The electrode may have no uninsulated sharp edges. The electrode may beconfigured to be spaced from a vessel wall surface.

In some examples, a system comprises a plurality of the devices. Theplurality of devices may at least partially form an electrode matrix.

In some examples, a device comprises or consists essentially of acatheter comprising a lumen, a fixation structure, and a fixationelement. The fixation structure comprises a first side, a second side,and a twist. The fixation element is coupled to the first side of thefixation structure. The first side faces radially inwardly when thefixation structure is inside the lumen of the catheter and facesradially outwardly when the fixation structure is outside the lumen ofthe catheter.

The lumen may be shaped to correspond to a shape of the fixationstructure and the fixation element. The twist may be 180°. The fixationstructure may comprise a ribbon. The fixation structure may comprise astrut. The fixation structure may be configured to bend radially outwardupon deployment from the catheter. The fixation element may comprise aconical spike.

In some examples, a device may comprise or consists essentially of afixation structure, a fixation mechanism, and an attachment pointcoupling the fixation structure to the fixation mechanism. The fixationmechanism is configured to turn radially outward upon expansion of thefixation structure. The fixation mechanism is configured to turnradially inward upon collapse of the fixation structure. In an expandedstate, the fixation mechanism extends radially outward of the fixationstructure.

The fixation mechanism may comprise an aperture. The device may furthercomprise a radiopaque marker coupled to the fixation mechanism.

The device may further comprise a tether extending proximally from theattachment point. Tether may comprise a bend along a longitudinal lengthof the fixation mechanism. The bend may be between 30% and 70% of thelongitudinal length of the fixation mechanism. The tether may comprise aramped portion having a wide edge coupled to the attachment point. Thetether may comprise a twist proximal to the attachment point.

The device may further comprise a second fixation mechanism extendingdistally from the fixation structure. The fixation structure, thefixation element, and the attachment point may be monolithically cutfrom a same hypotube. The fixation structure may comprise an electrode.The fixation structure may comprise a plurality of electrodes includingthe electrode. The plurality of electrodes may at least partially forman electrode matrix.

In some examples, a method of forming a device comprises or consistsessentially of cutting a hypotube to form a fixation structure, afixation mechanism, and an attachment point coupling the fixationstructure and the fixation mechanism, and shape setting an expandedshape. The expanded shape includes the fixation mechanism bent radiallyoutward of the fixation structure. After shape setting the expandedshape, the fixation mechanism is configured to turn radially outwardupon expansion of the fixation structure and the fixation mechanism isconfigured to turn radially inward upon collapse of the fixationstructure.

Cutting the hypotube may comprise laser cutting the hypotube. Cuttingthe hypotube may comprise forming a tether extending proximally from theattachment point. Shape setting may comprise bending the tether along alongitudinal length of the fixation mechanism. Bending the tether may bebetween 30% and 70% of the longitudinal length of the fixationmechanism. Shape setting may comprise bending the tether at a proximalend of the attachment point. Shape setting may comprise forming a twistin the tether proximal to the attachment point.

In some examples, a device comprises or consists essentially of afixation structure, a fixation arm, and a fixation mechanism coupled tothe fixation arm. The fixation structure comprises an aperture, a firstsurface, and a second surface opposite the first surface. The fixationarm is coupled to an inside of the aperture of the fixation structure.The fixation arm does not protrude above the first surface in a firststate.

The fixation arm may be configured to flex radially outward when notconfined by a catheter. The fixation mechanism may protrude above thefirst surface when the fixation arm is not confined by the catheter. Thefixation arm may be configured to remain stationary when not confined bya catheter. The fixation mechanism may not protrude above the firstsurface when the fixation arm may be not confined by the catheter.

The fixation structure and the fixation arm may be formed from a samepiece of material. The aperture may extend from the first surface to thesecond surface. The aperture may extends from the first surface to apoint above the second surface. The fixation mechanism may comprise aconical spike. The fixation mechanism may comprise a textured surface.

In some examples, a device comprises or consists essentially of acatheter comprising a lumen, a first loop longitudinally movable from inthe lumen of the catheter to out of the lumen of the catheter, and asecond loop longitudinally movable from in the lumen of the catheter toout of the lumen of the catheter. At least one of the catheter, thefirst loop, and the second loop comprises a first electrode. At leastone of the first loop and the second loop may be a pigtail at an end ofa finger.

The first loop may comprise a first plurality of electrodes includingthe first electrode. The first plurality of electrodes may at leastpartially form a first electrode matrix. The second loop may comprise asecond plurality of electrodes. The second plurality of electrodes mayat least partially form a second electrode matrix. The second loop maycomprise a second electrode.

The first loop may comprise a first portion comprising electrodes of thefirst plurality of electrodes and a second portion comprising electrodesof the first plurality of electrodes. The second portion may be spacedfrom the first portion. The second portion may be parallel to the firstportion.

The first loop may comprise an undulating segment comprising peaks andtroughs. The undulating segment may comprise the first plurality ofelectrodes. The undulating segment may comprise electrodes of the firstplurality of electrodes proximate to the peaks and electrodes of thefirst plurality of electrodes proximate to the troughs.

The catheter may comprise a plurality of electrodes including the firstelectrode. The first plurality of electrodes may at least partially forma first electrode matrix.

The first loop and the second loop may be configured to be deployed fromthe lumen of the catheter at least partially simultaneously. The firstloop and the second loop may be configured to be deployed from the lumenof the catheter sequentially.

The device may further comprise a fixation feature extending radiallyoutward from the catheter. The fixation feature may comprise anatraumatic stiff loop.

In some examples, a method of using the device may comprise or consistessentially of advancing the catheter distal to a pulmonary valve,advancing the catheter distal to the pulmonary valve, deploying thefirst loop and the second loop, and after deploying the first loop andthe second loop, distally advancing the catheter towards a pulmonaryartery bifurcation. The first loop and the second loop areself-orienting so that one of the first loop and the second loop extendsinto the right pulmonary artery and the other of the first loop and thesecond loop extends into the left pulmonary artery.

The method may further comprise distally advancing the catheter untiladvancement may be limited by the pulmonary artery bifurcation. Themethod may further comprise extending a fixation feature proximate tothe pulmonary valve. The method may further comprise attempting tocapture a target nerve with the first electrode.

The method may further comprise, if the target nerve may be notcaptured, withdrawing the first loop and the second loop into the lumenof the catheter, proximally retracting the catheter, rotating thecatheter, after rotating the catheter, redeploying the first loop andthe second loop, and, after redeploying the first loop and the secondloop, distally advancing the catheter towards the pulmonary arterybifurcation. The first loop and the second loop are self-orienting sothat one of the first loop and the second loop extends into the rightpulmonary artery and the other of the first loop and the second loopextends into the left pulmonary artery in an opposite orientation. Themethod may further comprise, if the target nerve may be not captured,attempting to capture a target nerve with a second electrode.

In some examples, a device comprises, or alternatively consistsessentially of, a catheter comprising a lumen and a loop longitudinallymovable from in the lumen of the catheter to out of the lumen of thecatheter. At least one of the catheter and the loop comprises a firstelectrode.

The loop may comprise a first plurality of electrodes including thefirst electrode. The first plurality of electrodes may at leastpartially form a first electrode matrix.

The loop may comprise a first portion comprising electrodes of the firstplurality of electrodes and a second portion comprising electrodes ofthe first plurality of electrodes. The second portion may be spaced fromthe first portion. The second portion may be parallel to the firstportion.

The loop may comprise an undulating segment comprising peaks andtroughs. The undulating segment may comprise the first plurality ofelectrodes. The undulating segment may comprise electrodes of the firstplurality of electrodes proximate to the peaks and electrodes of thefirst plurality of electrodes proximate to the troughs.

The catheter may comprise a first plurality of electrodes including thefirst electrode. The first plurality of electrodes may at leastpartially form a first electrode matrix.

The loop may be configured to be deployed from the lumen of the catheterout of a distal end of the catheter. The loop may be configured to bedeployed from the lumen of the catheter out of a side of the catheter.

The device may further comprise a fixation feature extending radiallyoutward from the catheter. The fixation feature may comprise anatraumatic stiff loop.

The loop may be a pigtail at an end of a finger.

A method of using the device may comprise deploying the loop out of thelumen of the catheter; after deploying the loop, advancing the catheterin a first branch vessel towards a primary vessel; allowing the loop toradially expand at a bifurcation comprising the first branch vessel, theprimary vessel, and a second branch vessel; and after allowing the loopto radially expand, proximally retracting the catheter until the loopcontacts the second branch vessel.

The first branch vessel may comprise the left internal jugular vein, theprimary vessel may comprise the left brachiocephalic vein, and thesecond branch vessel may comprise the left subclavian vein.

The method may further comprise extending a fixation feature.

The method may further comprise attempting to capture a target nervewith the first electrode. The target nerve may comprise a thoraciccardiac branch nerve. The target nerve may comprise a cervical cardiacnerve.

The catheter may comprise a curvature configured to bend towards thetarget nerve.

In some examples, a device comprises or consists essentially of acatheter comprising a lumen, a first sinusoidal wire, a secondsinusoidal wire radially spaced from the first sinusoidal wire, and aplurality of electrodes.

Each of the plurality of electrodes may be coupled to at least one thefirst sinusoidal wire and the second sinusoidal wire.

The device may further comprise a membrane coupled to the firstsinusoidal wire and the second sinusoidal wire. Each of the plurality ofelectrodes may be coupled to the membrane. The membrane may beconfigured to have a curved shape in an expanded state. The membrane maycomprise a flex circuit including conductor wires.

The plurality of electrodes may comprise button electrodes. Theplurality of electrodes may comprise barrel electrodes. The plurality ofelectrodes may comprise cylindrical electrodes. The plurality ofelectrodes may comprise directional electrodes. Centers the plurality ofelectrodes may be longitudinally offset.

The catheter may comprise a first segment and a second segment distal tothe first segment. The first segment may have a circular cross-section.The second segment may have an oval cross-section. The second segmentmay be configured to contain the first sinusoidal wire and the secondsinusoidal wire.

The first sinusoidal wire and the second sinusoidal wire may be planarin an expanded state. The first sinusoidal wire and the secondsinusoidal wire may be at an angle in an expanded state. The firstsinusoidal wire and the second sinusoidal wire may comprise shape memorymaterial.

In some examples, a device comprises, or alternatively consistsessentially of, a handle, a sheath, and an electrode system moveable inand out of the sheath. The handle comprises a repositioning system. Therepositioning system comprises a track and a knob slideable within thetrack. The electrode system is configured to move longitudinally uponlongitudinal movement of the knob in the track and to move rotationallyupon transverse or rotational movement of the knob in the track.

The track may comprise a longitudinal segment, a first transversesegment extending from the longitudinal segment in a first direction,and a second transverse segment extending from the longitudinal segmentin a second direction opposite the first direction. The first transversesegment may be longitudinally offset from the second transverse segment.The first transverse segment may be longitudinally aligned with thesecond transverse segment.

The electrode system may be configured to move a longitudinal distanceupon movement of the knob the same longitudinal distance in the track.The electrode system may be configured to rotate a circumferential angleupon transverse or rotational movement of the knob in the track. Thedevice may further comprise a rotational stop to limit rotation of theelectrode system to the circumferential angle.

The device may further comprise a detent and a groove configured tointeract with the detent upon movement of the knob. The detent may beconfigured to produce audible indicia.

The device may further comprise a physical barrier configured to inhibitaccidental movement of the knob.

In some examples, a device comprises, or alternatively consistsessentially of, an expandable structure having a collapsed state and anexpanded state. The expandable structure comprises, in the expandedstate, a plurality of splines each comprising a proximal segmentcomprising a first portion, a second portion distal to the firstportion, and a third portion distal to the second portion; anintermediate segment distal to the proximal segment; and a distalsegment distal to the intermediate segment, the distal segmentcomprising a fourth portion, a fifth portion distal to the fourthportion, and a sixth portion distal to the fifth portion. The firstportion is parallel to a longitudinal axis. The second portion extendsradially outward from the first portion. The third portion extendsradially outward from the second portion and transverse to thelongitudinal axis to the intermediate segment. The fourth portionextends from the intermediate segment radially inward and transverse tothe longitudinal axis. The fifth portion extends radially inward fromthe fourth portion. The sixth portion extends from the fifth portionparallel to a longitudinal axis. At least two of the intermediatesegments of the plurality of splines are circumferentially spaced andcomprise a plurality of electrodes forming an electrode matrix.

The expandable structure may be self-expanding. The expandable structuremay be expandable upon operation of an actuation mechanism.

In the expanded state, the at least two intermediate segments may beparallel to the longitudinal axis. In the expanded state, the at leasttwo intermediate segments may be recessed relative to the longitudinalaxis. In the expanded state, the at least two intermediate segments maybe crowned relative to the longitudinal axis.

Pairs of the first portions of the plurality of splines may be parallel.Pairs of the sixth portions of the plurality of splines may be parallel.Pairs of the first portions of the plurality of splines may be twisted.Pairs of the sixth portions of the plurality of splines may be twisted.

Proximal ends of the intermediate segments of the plurality of splinesmay be longitudinally aligned. Proximal ends of the intermediatesegments of the plurality of splines may be longitudinally offset.Distal ends of the intermediate segments of the plurality of splines maybe longitudinally aligned. Distal ends of the intermediate segments ofthe plurality of splines may be longitudinally offset.

The plurality of splines may further comprise a spline circumferentiallybetween the at least two intermediate segments.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The expandable structure may further comprise a membrane coupled to theat least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the expandable structure. Theexpandable structure may be configured to expand upon operation of theactuator mechanism. The proximal portion may comprise a Y-connectorcomprising a first branch configured to accept a guidewire and a secondbranch configured to electrically connect the electrode matrix to astimulation system.

The device may further comprise a strain relief between the cathetershaft and the expandable structure. The strain relief may comprise aspring. The strain relief may comprise a cut hypotube. The cut hypotubemay comprise a plurality of helices having the same sense.

The expandable structure may comprise a distal hub comprising aplurality of channels. The distal segments of the plurality of splinesmay be slideable in the channels of the distal hub. The distal segmentsmay comprise a distal end having a dimension larger than a dimension ofthe channels.

In some examples, a device comprises, or alternatively consistsessentially of, an expandable structure having a collapsed state and anexpanded state. The expandable structure comprises, in the expandedstate, a plurality of arms each comprising a proximal segment, anintermediate segment distal to the proximal segment, and a distalsegment distal to the intermediate segment. The intermediate segments ofthe plurality of arms include an opening. At least two the intermediatesegments of the plurality of splines comprise a plurality of electrodesforming an electrode matrix.

The expandable structure may be self-expanding. The expandable structuremay be expandable upon operation of an actuation mechanism.

In the expanded state, the at least two intermediate segments may beparallel to the longitudinal axis. In the expanded state, the at leasttwo intermediate segments may be recessed relative to the longitudinalaxis. In the expanded state, the at least two intermediate segments maybe crowned relative to the longitudinal axis.

Pairs of the first portions of the plurality of splines may be parallel.Pairs of the sixth portions of the plurality of splines may be parallel.Pairs of the first portions of the plurality of splines may be twisted.Pairs of the sixth portions of the plurality of splines may be twisted.

Proximal ends of the intermediate segments of the plurality of splinesmay be longitudinally aligned. Proximal ends of the intermediatesegments of the plurality of splines may be longitudinally offset.Distal ends of the intermediate segments of the plurality of splines maybe longitudinally aligned. Distal ends of the intermediate segments ofthe plurality of splines may be longitudinally offset.

The plurality of splines may further comprise a spline circumferentiallybetween the at least two intermediate segments.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The expandable structure may further comprise a membrane coupled to theat least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the expandable structure. Theexpandable structure may be configured to expand upon operation of theactuator mechanism. The proximal portion may comprise a Y-connectorcomprising a first branch configured to accept a guidewire and a secondbranch configured to electrically connect the electrode matrix to astimulation system.

The device may further comprise a strain relief between the cathetershaft and the expandable structure. The strain relief may comprise aspring. The strain relief may comprise a cut hypotube. The cut hypotubemay comprise a plurality of helices having the same sense.

The expandable structure may comprise a distal hub comprising aplurality of channels. The distal segments of the plurality of splinesmay be slideable in the channels of the distal hub. The distal segmentsmay comprise a distal end having a dimension larger than a dimension ofthe channels.

In some examples, a device comprises, or alternatively consistsessentially of, an expandable structure having a collapsed state and anexpanded state. The expandable structure comprises, in the expandedstate, a plurality of splines each comprising a proximal segmentcomprising a first portion, a second portion distal to the firstportion, and a third portion distal to the second portion; anintermediate segment distal to the proximal segment; and a distalsegment distal to the intermediate segment, the distal segmentcomprising a fourth portion, a fifth portion distal to the fourthportion, and a sixth portion distal to the fifth portion. The firstportion is parallel to a longitudinal axis. The second portion extendsradially outward from the first portion. The third portion extendsradially outward from the second portion and transverse to thelongitudinal axis to the intermediate segment. The fourth portionextends from the intermediate segment radially inward and transverse tothe longitudinal axis. The fifth portion extends radially inward fromthe fourth portion. The sixth portion extends from the fifth portionparallel to a longitudinal axis. The intermediate segments of theplurality of splines have an undulating shape relative to thelongitudinal axis. At least two of the intermediate segments of theplurality of splines comprise a plurality of electrodes forming anelectrode matrix.

The expandable structure may be self-expanding. The expandable structuremay be expandable upon operation of an actuation mechanism.

Pairs of the first portions of the plurality of splines may be parallel.Pairs of the sixth portions of the plurality of splines may be parallel.Pairs of the first portions of the plurality of splines may be twisted.Pairs of the sixth portions of the plurality of splines may be twisted.

Proximal ends of the intermediate segments of the plurality of splinesmay be longitudinally aligned. Proximal ends of the intermediatesegments of the plurality of splines may be longitudinally offset.Distal ends of the intermediate segments of the plurality of splines maybe longitudinally aligned. Distal ends of the intermediate segments ofthe plurality of splines may be longitudinally offset.

The intermediate segments may comprise peaks and troughs. Peaks andtroughs of the at least two intermediate segments may be longitudinallyaligned. Peaks and troughs of the at least two intermediate segments maybe longitudinally offset.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The expandable structure may further comprise a membrane coupled to theat least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the expandable structure. Theexpandable structure may be configured to expand upon operation of theactuator mechanism. The proximal portion may comprise a Y-connectorcomprising a first branch configured to accept a guidewire and a secondbranch configured to electrically connect the electrode matrix to astimulation system.

The device may further comprise a strain relief between the cathetershaft and the expandable structure. The strain relief may comprise aspring. The strain relief may comprise a cut hypotube. The cut hypotubemay comprise a plurality of helices having the same sense.

The expandable structure may comprise a distal hub comprising aplurality of channels. The distal segments of the plurality of splinesmay be slideable in the channels of the distal hub. The distal segmentsmay comprise a distal end having a dimension larger than a dimension ofthe channels.

In some examples, a device comprises, or alternatively consistsessentially of, an expandable structure having a collapsed state and anexpanded state. The expandable structure comprises, in the expandedstate, a plurality of arms each comprising a proximal segment, anintermediate segment distal to the proximal segment, and a distalsegment distal to the intermediate segment. The intermediate segments ofthe plurality of arms include a sinusoidal shape. At least two theintermediate segments of the plurality of splines comprise a pluralityof electrodes forming an electrode matrix.

The expandable structure may be self-expanding. The expandable structuremay be expandable upon operation of an actuation mechanism.

Pairs of the first portions of the plurality of splines may be parallel.Pairs of the sixth portions of the plurality of splines may be parallel.Pairs of the first portions of the plurality of splines may be twisted.Pairs of the sixth portions of the plurality of splines may be twisted.

Proximal ends of the intermediate segments of the plurality of splinesmay be longitudinally aligned. Proximal ends of the intermediatesegments of the plurality of splines may be longitudinally offset.Distal ends of the intermediate segments of the plurality of splines maybe longitudinally aligned. Distal ends of the intermediate segments ofthe plurality of splines may be longitudinally offset.

The intermediate segments may comprise peaks and troughs. Peaks andtroughs of the at least two intermediate segments may be longitudinallyaligned. Peaks and troughs of the at least two intermediate segments maybe longitudinally offset.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The expandable structure may further comprise a membrane coupled to theat least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the expandable structure. Theexpandable structure may be configured to expand upon operation of theactuator mechanism. The proximal portion may comprise a Y-connectorcomprising a first branch configured to accept a guidewire and a secondbranch configured to electrically connect the electrode matrix to astimulation system.

The device may further comprise a strain relief between the cathetershaft and the expandable structure. The strain relief may comprise aspring. The strain relief may comprise a cut hypotube. The cut hypotubemay comprise a plurality of helices having the same sense.

The expandable structure may comprise a distal hub comprising aplurality of channels. The distal segments of the plurality of splinesmay be slideable in the channels of the distal hub. The distal segmentsmay comprise a distal end having a dimension larger than a dimension ofthe channels.

In some examples, a device comprises, or alternatively consistsessentially of, a longitudinal axis and a distal portion. The distalportion comprises a first expandable structure and a second expandablestructure distal to the first expandable structure. The first expandablestructure has a collapsed state and an expanded state. The expandablestructure comprises, in the expanded state, a plurality of arms eachcomprising a proximal segment, an intermediate segment distal to theproximal segment, and a distal segment distal to the intermediatesegment. The plurality of arms is on a first side of a plane comprisingthe longitudinal axis. At least two the intermediate segments of theplurality of splines comprise a plurality of electrodes forming anelectrode matrix; and

The second expandable structure may comprise a Swan-Ganz balloon. Thesecond expandable structure may be distal to the first expandablestructure by between 0.25 cm and 5 cm.

The first expandable structure may be self-expanding. The firstexpandable structure may be expandable upon operation of an actuationmechanism.

The plurality of splines may comprise a plurality of wires. Theplurality of splines may be formed from a cut hypotube.

The first expandable structure may further comprise a membrane coupledto the at least two intermediate segments. The membrane may comprise theelectrode matrix.

The device may further comprise a proximal portion and a catheter shaftcoupled to the proximal portion and coupled to the expandable structure.The catheter shaft may be configured to appose a wall of a body cavity.The device may further comprise an actuator wire. The proximal portionmay comprise an actuator mechanism. The actuator wire may be coupled tothe actuator mechanism and coupled to the first expandable structure.The first expandable structure may be configured to expand uponoperation of the actuator mechanism. The proximal portion may comprise aY-connector comprising a first branch configured to accept a guidewireand a second branch configured to electrically connect the electrodematrix to a stimulation system.

The first expandable structure may comprise a distal hub comprising aplurality of channels. Distal segments of the plurality of splines maybe slideable in the channels of the distal hub. The distal segments maycomprise a distal end having a dimension larger than a dimension of thechannels.

The device may further comprise a tubular member extending from theproximal portion to the second expandable structure. The tubular membermay comprise a lumen configured to inflate the second expandablestructure upon injection of fluid into the lumen. The tubular member maybe coupled to the distal segments of the plurality of arms. The firstexpandable structure may expand upon proximal retraction of the tubularmember.

In some examples, a method of processing an electrocardiogram signalcomprising P waves and S waves comprises, or alternatively consistessentially of, detecting an end of a first S wave, estimating a startof a first P wave, and during a stimulation duration between detectingthe end of the first S wave and the estimated start of the first P wave,providing an artificial signal. A non-transitory computer-readablemedium may store executable instructions that when executed perform themethod.

The artificial signal may comprise a straight line. The straight linemay be at a negative value. The straight line may be at a positivevalue.

In some examples, an electrocardiogram signal comprises, oralternatively consist essentially of, a first portion indicative of anelectrical activity of a heart during a first duration and a secondportion not indicative of the electrical activity of the heart during asecond duration after the first duration. The first duration is lessthan a sinus rhythm. A non-transitory computer-readable medium may beconfigured to store the signal.

The first portion may comprise a QRS complex. The first portion maycomprise a PR interval. The second portion may comprise a ST segment.The second portion may comprise a straight line. The straight line maybe at a negative value. The straight line may be at a positive value.

In some examples, a method of processing an electrocardiogram signalcomprises, or alternatively consist essentially of, detecting a firstcondition of a first type of wave selected from the group consisting ofP waves, Q waves, R waves, S waves, and T waves; after a stimulationduration starting after detecting the first condition of the first typeof wave, monitoring for a monitoring duration for second condition of asecond type of wave selected from the group consisting of P waves, Qwaves, R waves, S waves, and T waves, the second type of wave differentthan the first type of wave; and if the second condition of the secondtype of wave may be not detected during the monitoring duration,triggering a physical event. A non-transitory computer-readable mediummay store executable instructions that when executed perform the method.

The first condition may comprise a beginning of the first type of wave.The first condition may comprise an end of the first type of wave. Thefirst condition may comprise a peak of the first type of wave. Thesecond condition may comprise a beginning of the second type of wave.The second condition may comprise an end of the second type of wave. Thesecond condition may comprise a peak of the second type of wave. Thesecond condition may comprise a peak of the second type of wave. Thefirst type of wave may comprise a S wave. The second type of wave maycomprise a P wave. The second type of wave may comprise a Q wave. Thesecond type of wave may comprise a R wave. The physical event maycomprise terminating stimulation. The physical event may comprisesounding an alarm (e.g., sending a wireless message).

In some examples, a method of processing an electrocardiogram signalcomprises, or alternatively consist essentially of, providing a firstportion indicative of electrical activity of a heart during a firstduration, the first portion comprising a real P wave, a real Q wave, areal R wave, a real S wave, and a real T wave; and providing a secondportion not indicative of the electrical activity of the heart during asecond duration after the first duration, stimulation of the heartoccurring during the second duration. A non-transitory computer-readablemedium may store executable instructions that when executed perform themethod.

The portion may comprise a straight line. The straight line may be atzero. The straight line may be at a negative value. The straight linemay be at a positive value.

The second portion may comprise a duplication of the first portion.

The second portion may comprise at least a portion of an artificialsinus rhythm. The portion of the artificial sinus rhythm may comprise atleast one of an artificial P wave, an artificial Q wave, an artificial Rwave, an artificial S wave, and an artificial T wave. The at least oneof an artificial P wave, an artificial Q wave, an artificial R wave, anartificial S wave, and an artificial T wave may be shaped like a realwave. The at least one of an artificial P wave, an artificial Q wave, anartificial R wave, an artificial S wave, and an artificial T wave may beshaped like a square wave.

In some examples, an electrocardiogram signal comprises, oralternatively consist essentially of, a first portion indicative ofelectrical activity of a heart during a first duration and a secondportion not indicative of the electrical activity of the heart during asecond duration after the first duration. The first portion comprisies areal P wave, a real Q wave, a real R wave, a real S wave, and a real Twave. Stimulation of the heart occurs during the second duration. Anon-transitory computer-readable medium may be configured to store thesignal.

The second portion may comprise a straight line. The straight line maybe at zero. The straight line may be at a negative value. The straightline may be at a positive value.

The second portion may comprise a duplication of the first portion.

The second portion may comprise at least a portion of an artificialsinus rhythm.

The portion of the artificial sinus rhythm may comprise at least one ofan artificial P wave, an artificial Q wave, an artificial R wave, anartificial S wave, and an artificial T wave. The at least one of anartificial P wave, an artificial Q wave, an artificial R wave, anartificial S wave, and an artificial T wave may be shaped like a realwave. The at least one of an artificial P wave, an artificial Q wave, anartificial R wave, an artificial S wave, and an artificial T wave may beshaped like a square wave.

In some examples, a device comprises, or alternatively consistsessentially of, a handle, an expandable structure, an outer tube, and ashaft. The expandable structure has a collapsed state and aself-expanded state. The expandable structure comprises a plurality ofsplines extending from a proximal hub to a distal hub. Each of thesplines of the plurality of splines comprises a proximal segment, anintermediate segment distal to the proximal segment, a distal segmentdistal to the intermediate segment, and a first electrode on a firstspline of the plurality of splines. The intermediate segment isconfigured to extend radially outward in the self-expanded state. Theouter tube comprises a proximal end coupled to the handle and a distalend coupled to the proximal hub. The shaft comprises a proximal end anda distal end. The shaft extends through the outer tube from the handleto the distal hub. The handle is configured to retract the shaft. Theintermediate segments are configured to extend further radially outwardupon retraction of the shaft.

At least one spline of the plurality of splines may be devoid ofelectrodes. The intermediate segment of each spline of the plurality ofsplines may form a first angle with the proximal segment and/or a secondangle with the distal segment. The proximal segment and distal segmentof each spline of the plurality of splines may be devoid of electrodes.The first spline may comprise a first plurality of electrodes includingthe first electrode. The first plurality of electrodes may form anelectrode array. The device may further comprise a second electrode on asecond spline of the plurality of splines. The first spline may comprisea first plurality of electrodes including the first electrode. Thesecond spline may comprise a second plurality of electrodes includingthe second electrode. The first plurality of electrodes may comprisefive electrodes. The second plurality of electrodes may comprise fiveelectrodes. The first plurality of electrodes and the second pluralityof electrodes form an electrode array. The second spline may becircumferentially adjacent to the first spline. The first spline and thesecond spline may form a first spline pair. The device may furthercomprise a second spline pair. The second spline pair may comprise athird spline comprising a third plurality of electrodes and a fourthspline comprising a fourth plurality of electrodes. The fourth splinemay be circumferentially adjacent to the third spline. The second splinepair may be circumferentially adjacent to the first spline pair. Thefirst plurality of electrodes, the second plurality of electrodes, thethird plurality of electrodes, and the fourth plurality of electrodesmay form an electrode array. The electrode array may comprise a 4×5array. At least four circumferentially adjacent splines of the pluralityof splines may each comprise a plurality of electrodes. At least onespline of the plurality of splines may be devoid of electrodes. Theproximal segment and distal segment of each spline may be straight. Theintermediate segment of each spline may be concave. The proximal segmentand distal segment of each spline may be straight. The intermediatesegment of each spline may be convex. The proximal segment and distalsegment of each spline may be straight. The intermediate segment of eachspline may be straight. Each spline of the plurality of splines furthermay comprise a proximal transition segment joining the proximal segmentand the intermediate segment and a distal transition segment joining theintermediate segment and the distal segment. The splines may be groupedinto circumferentially adjacent spline pairs. Each spline of a splinemay be parallel to the other spline of the spline pair along theproximal segment, the intermediate segment, and the distal segment. Eachspline of the spline pair may be not parallel to the other spline of thespline pair along the proximal transition segment and the distaltransition segment. The intermediate segments of each spline pair may bespaced further apart from each other than the proximal segments and thedistal segments. The expandable structure may comprise a longitudinalaxis between the proximal hub and the distal hub. The proximal segmentsof each of the splines of the plurality of splines may radially divergeaway from the longitudinal axis and the distal segments of each of thesplines of the plurality of splines may radially converge towards thelongitudinal axis.

The outer tube may comprise a proximal portion and a distal portion. Theproximal portion may have a higher durometer than the distal portion.The outer tube may comprise a plurality of longitudinal portions along alength of the outer tube. Each longitudinal portion the plurality oflongitudinal portions may have a higher durometer than the longitudinalportions of the plurality of longitudinal portions distal thereto. Atleast one longitudinal portion of the plurality of longitudinal portionsmay be configured with a length and durometer for positioning the atleast one longitudinal portion in a specific anatomy. The specificanatomy may comprise a chamber of a heart. The specific anatomy maycomprise a blood vessel. The blood vessel may comprise the rightpulmonary artery. The outer tube may comprise a first outer diameter atthe proximal end of the outer tube and a second outer diameter at thedistal end of the outer tube. The first outer diameter may be greaterthan the second outer diameter. A proximal portion of the outer tube maycomprise a first plurality of layers, wherein a distal portion of theouter tube may comprise a second plurality of layers. The firstplurality of layers may comprise more layers than the second pluralityof layers. The outer tube may comprise a hinge joined to the proximalhub. The hinge may be configured to resist kinking upon bending of thedevice transverse to a longitudinal axis of the outer tube. The hingemay comprise a coil comprising a proximal end and a distal end, theproximal end of the coil surrounding a portion of the tubing and thedistal end of the coil surrounding a portion of the proximal hub. Thehinge may comprise a first wire comprising a helical winding, a secondwire comprising a helical winding and occupying spaces between helicesof the first wire, and a third wire comprising a helical winding andoccupying spaces between helices the first wire and between helices ofthe second wire. The outer tube may comprise tubing. The tubing maycomprise an inner diameter configured to mate with an outer diameter ofthe proximal hub. The tubing may be configured to abut a proximal end ofthe proximal hub. The tubing may form a fluid seal between the outertube and the proximal hub.

The spline comprising the electrode may comprise a spline tube, theelectrode being on an outer surface of the spline tube. The device mayfurther comprise a spline tube at least partially covering twocircumferentially adjacent splines of the plurality of splines. Thespline tube may be configured to inhibit the two circumferentiallyadjacent splines from rotating relative to one another. The spline tubemay diverge into two spatially separated tubular channels along theintermediate segments of the two circumferentially adjacent splines.Circumferentially adjacent splines of the plurality of splines may begrouped into spline pairs, each of the spline pairs comprising aproximal tubing at least partially covering the proximal segments and adistal tubing at least partially covering the distal segments. Theproximal tubings and the distal tubings may be configured to inhibit thesplines of each of the spline pairs from rotating relative to oneanother. Each of the proximal tubings and the distal tubings maycomprise heat-shrink tubing. Circumferentially adjacent splines of theplurality of splines may be grouped into spline pairs, each of thespline pairs comprising a wire bent at a proximal end, and may have wireends terminating at a distal end.

The proximal hub may comprise a proximal end, a distal end, a centrallumen, a plurality of peripheral lumens, and/or a plurality of splinechannels. The central lumen may extend from the proximal end of theproximal hub to the distal end of the proximal hub. The shaft mayslidably extend through the central lumen of the proximal hub. Theplurality of peripheral lumens may be radially outward of the centrallumen of the proximal hub. The plurality of peripheral lumens may beconfigured to transfer fluid flowing through the outer tube to thedistal end of the proximal hub. The plurality of spline channels mayextend proximally from the distal end of the proximal hub into a distalportion of the proximal hub. One spline of the plurality of splines maybe in each spline channel of the plurality of spline channels of theproximal hub. The plurality of spline channels may extend through thedistal portion of the proximal hub. Circumferentially adjacent splinesof the plurality of splines may be grouped into spline pairs, each ofthe spline pairs comprising a wire bent at a proximal end. The proximalhub may comprise a plurality of recesses proximal to the distal portionof the proximal hub. The bent proximal ends of the wire of each of thespline pairs may be in a recess of the plurality of recesses. Theplurality of recesses may be configured to inhibit movement of theplurality of splines proximal to the recesses. At least one peripherallumen of the plurality of peripheral lumens may be configured to receivean electrical conductor extending from the handle to the electrode.

The distal hub may comprise a proximal end, a distal end, a centrallumen, and/or a plurality of spline channels. The central lumen mayextend from the proximal end of the distal hub to the distal end of thedistal hub. The shaft may be fixably coupled to the central lumen of thedistal hub. A plurality of spline channels may extend distally from theproximal end of the distal hub into the distal hub. One spline of theplurality of splines may be in each spline channel of the plurality ofspline channels of the distal hub. Each spline channel of the pluralityof spline channels of the distal hub may terminate proximal to thedistal end of the distal hub. The proximal end of the distal hub maycomprise a tapered surface. The tapered surface of the proximal end ofthe distal hub may comprise openings to the plurality of splinechannels. The tapered surface proximal end of the distal hub may beconfigured to facilitate bending of the splines in a radially outwarddirection. The distal end of the distal hub may comprise an atraumaticconfiguration.

The handle may comprise a handle base and an actuator. The handle basemay comprise a proximal end, a distal end, and a lumen extending fromthe proximal end to the distal end. A proximal end of the outer tube maybe coupled to the lumen of the handle base, the shaft slidably extendingthrough the lumen of the handle base. An actuator may be affixed to aproximal end of the shaft, the actuator moveable relative to the handlebase in a proximal direction and in a distal direction. The actuator maybe configured to expand the expandable structure when moved in a distaldirection and to compress the expandable structure when moved in aproximal direction. The handle further may comprise an outer handle, asecuring member, and/or a locking member. The outer handle may extendfrom the handle base. The securing member may comprise a proximal endaffixed to the actuator. The locking member may be positioned along thesecuring member between the outer handle and the actuator. The lockingmember may be configured to be moved along the longitudinal axis of thesecuring member and secured at a position along a length of the securingmember to inhibit movement of the actuator in a distal direction. Thesecuring member may comprise a threaded shaft and the locking member maycomprise a threaded channel. The locking member may be longitudinallymoveable along the securing member by rotating the locking member aroundthe threaded shaft.

The handle may comprise a locking member having a locked configurationand an unlocked configuration. The locking member may comprise a mainbody comprising a proximal end and a distal end, a channel extendingfrom the proximal end to the distal end, and a protrusion extending intothe channel of the locking member. The actuator may extend through thechannel of the locking member. The protrusion may be configured toinhibit the actuator from moving in at least one of a proximal directionand a distal direction relative to the handle base when the lockingmember is in the locked configuration. The actuator may be moveable inthe proximal direction and in the distal direction when the lockingmember is in the unlocked configuration. The actuator may comprise anelongate body and a textured surface along a length of the elongatebody. The locking member may be moveable between the lockedconfiguration and the unlocked configuration by rotating the lockingmember around the elongate body of the actuator. The protrusion may beconfigured to interface with the textured surface in a locked positionand configured to not interface with the textured surface in theunlocked position. The locking member may further comprise a tabextending away from the main body, the tab being positionable in a firstposition relative to the handle base when the locking member is in alocked configuration and being positionable in a second position whenthe locking member is in an unlocked configuration. The textured surfacemay comprise a series of ridges, the protrusion of the locking memberconfigured to mate with a notch between the ridges. The channel of thelocking member may be oblong. The locking member may be configured toswitch between a locked configuration and an unlocked configuration byrotating the locking member approximately a quarter turn. The handlebase may further comprise an aperture in a sidewall extending into thelumen of the handle base and proximal to the proximal end of the outertube. An electrical conductor may extend from an electrical socket intothe outer tube through the aperture of the handle base.

The shaft may comprise a lumen. The lumen of the shaft may be configuredto receive a guidewire. A proximal end of the shaft may be configured toreceive fluid. The proximal end of the shaft may be joined to a fluidvalve. The shaft may comprise a sidewall and an aperture in thesidewall, the aperture configured to permit fluid to flow out of thelumen of the shaft and to the proximal hub. The device may be configuredto transfer fluid injected into the shaft through the shaft to thedistal hub and through the outer tube to the proximal hub. The shaft maycomprise a plurality of hypotubes. The plurality of hypotubes maycomprise a first hypotube having a proximal end and a distal end and asecond hypotube having a proximal end and a distal end. The distal endof the first hypotube may be in the proximal end of the second hypotube.The proximal end of the second hypotube may be in the distal end of thefirst hypotube. The plurality of hypotubes may include three hypotubes.At least one hypotube of the plurality of hypotubes may comprise aproximal portion having a first outer diameter and a distal portionhaving a second outer diameter less than the first outer diameter. Atleast one hypotube of the plurality of hypotubes may comprise a sidewalland an aperture through the sidewall.

In some examples, a method of modulating a nerve comprises, oralternatively consists essentially of, inserting a distal portion of adevice comprising an expandable structure into vasculature, allowing theexpandable member to self-expand, actuating a handle of the device tofurther expand the expandable structure to anchor the expandablestructure in the vasculature, and activating a first electrode of thedevice to stimulate the nerve. The device comprises a proximal portioncomprising the handle and the distal portion comprising the expandablestructure. The expandable structure has a collapsed state and aself-expanded state. The expandable structure comprises a plurality ofsplines extending from a proximal hub to a distal hub. Each of thesplines of the plurality of splines comprises a proximal segment, anintermediate segment distal to the proximal segment, and a distalsegment distal to the intermediate segment. The intermediate segment isconfigured to extend radially outward in the self-expanded state. Theexpandable structure comprises a first electrode on a first spline ofthe plurality of splines.

The device may comprise an outer tube and a shaft. The outer tube maycomprise a proximal end coupled to the handle and a distal end coupledto the proximal hub. The shaft may comprise a proximal end and a distalend and may extend through the outer tube from the handle to the distalhub. The handle may be configured to retract the shaft in a proximaldirection relative to the outer tube when the handle is actuated,causing the distal hub and the proximal hub to move closer together.

The method may further comprise accessing the vasculature with a needleand a syringe. The method may further comprise inserting a guidewireinto the vasculature. The shaft of the device may comprise a lumenextending from the proximal portion of the device to the distal portionof the device. The insertion of the distal portion of the device intothe vasculature may comprise inserting the device over the guidewiresuch that the guidewire may be slidably received in the lumen of theshaft. The method may further comprise tracking the guidewire to atarget location in the vasculature. The method may further compriseinserting a Swan-Ganz catheter into vasculature. The Swan-Ganz cathetermay comprise an inflatable balloon at a distal end of the catheter. Themethod may further comprise inflating the inflatable balloon, allowingthe balloon to be carried by blood flow to the target location,inserting the guidewire through a lumen in the Swan-Ganz catheter to thetarget location, deflating the inflatable balloon, and retracting theSwan-Ganz catheter from the vasculature. The target location may be theright pulmonary artery.

The method may further comprise inserting an introducer in thevasculature. The insertion of the distal portion of the medical deviceinto the vasculature may comprise inserting the device through a sheathof the introducer. The method may further comprise retracting a distalend of the introducer sheath from the distal portion of the deviceand/or pushing the distal portion of the device beyond the distal end ofthe sheath, causing the expandable structure to self-expand. The methodmay further comprise actuating a locking member on the handle to preventthe expandable structure from being compressed. The method may furthercomprise positioning the expandable structure in the right pulmonaryartery. The nerve may be a cardiopulmonary nerve. The expandablestructure may further comprise a second electrode on a second spline ofthe plurality of splines, the expandable structure being positioned suchthat the nerve may be positioned along the first spline, along thesecond spline, or between the first spline and the second spline. Themethod may further comprise activating the second electrode. The firstspline may be circumferentially adjacent the second spline. The firstspline may comprise a first plurality of electrodes including the firstelectrode, and the second spline may comprise a second plurality ofelectrodes including the second electrode. The first plurality ofelectrodes may comprise five electrodes and the second plurality ofelectrodes may comprise five electrodes. The first spline and the secondspline may form a first spline pair. The first plurality of electrodesand the second plurality of electrodes may form an electrode array. Theexpandable structure may further comprise a second spline paircomprising a third spline comprising a third plurality of electrodes anda fourth spline comprising a fourth plurality of electrodes. The firstplurality of electrodes, the second plurality of electrodes, the thirdplurality of electrodes, and the fourth plurality of electrodes may forman electrode array. The electrode array may comprise a 4×5 array. Themethod may further comprise positioning the expandable structure againsttissue in the vasculature so that the nerve may be between at least twoelectrodes apposed against the tissue. The nerve may be between at leastthree electrodes apposed against the tissue. The nerve may be between atleast four electrodes apposed against the tissue. Activating the firstelectrode may comprise applying a voltage pulse of a first polarity. Themethod may further comprise applying a pre-pulse of voltage to tissuesurrounding the nerve prior to activating the first electrode, thepre-pulse being a second polarity opposite the first polarity. Themethod may further comprise measuring the pressure in the rightventricle and approximating the pressure in the left ventricle from themeasured pressure in the right ventricle. The method may furthercomprise positioning a return conductor in the vasculature or on skin,the return conductor configured to conduct current from the activatedelectrode.

In some examples, a device for increasing heart contractility fortreating heart failure comprises, or alternatively consists essentiallyof, a handle, and an expandable structure. The expandable structure hasa collapsed state and a self-expanded state. The expandable structurecomprises a plurality of splines extending from a proximal hub to adistal hub. The device further comprises a first electrode on a firstspline of the plurality of splines, an outer tube extending from thehandle to the proximal hub, and a shaft extending through the outer tubefrom the handle to the distal hub. The handle is configured to retractthe shaft. The device is configured for placement in a pulmonary arteryand delivery of energy from the first electrode to a target tissue toincrease heart contractility for treating heart failure.

At least one spline of the plurality of splines may be devoid ofelectrodes.

The first spline may comprise a first plurality of electrodes includingthe first electrode. The first plurality of electrodes may form anelectrode array.

The device may further comprise a second electrode on a second spline ofthe plurality of splines. The first spline may comprise a firstplurality of electrodes including the first electrode. The second splinemay comprise a second plurality of electrodes including the secondelectrode. The first plurality of electrodes may comprise fiveelectrodes. The second plurality of electrodes may comprise fiveelectrodes. The first plurality of electrodes and the second pluralityof electrodes may form an electrode array. The second spline may becircumferentially adjacent to the first spline. The first spline and thesecond spline may form a first spline pair. The device may furthercomprise a second spline pair comprising a third spline comprising athird plurality of electrodes and a fourth spline comprising a fourthplurality of electrodes. The fourth spline may be circumferentiallyadjacent to the third spline. The second spline pair may becircumferentially adjacent to the first spline pair. The first pluralityof electrodes, the second plurality of electrodes, the third pluralityof electrodes, and the fourth plurality of electrodes form an electrodearray. The electrode array may comprise a 4 x 5 array. Each of at leastfour circumferentially adjacent splines of the plurality of splines maycomprise a plurality of electrodes.

Each of the splines of the plurality of splines may comprise a proximalsegment, an intermediate segment distal to the proximal segment, and adistal segment distal to the intermediate segment. The intermediatesegments may be configured to extend radially outward in theself-expanded state. The intermediate segments may be configured toextend further radially outward upon retraction of the shaft. Theintermediate segment of each spline of the plurality of splines may forma first angle with the proximal segment and a second angle with thedistal segment. The intermediate segment of each spline of the pluralityof splines may curve into the proximal segment and the distal segment.

The proximal segment and the distal segment of each spline of theplurality of splines may be devoid of electrodes.

The proximal segment and the distal segment of each spline may bestraight. The intermediate segment of each spline may be concave. Theintermediate segment of each spline may be convex. The intermediatesegment of each spline may be straight. Each of the proximal segment,the distal segment, and intermediate segment of each spline may bearcuate.

Each spline of the plurality of splines may further comprise a proximaltransition segment joining the proximal segment and the intermediatesegment, and a distal transition segment joining the intermediatesegment and the distal segment. Each spline of the spline pair may benot parallel to the other spline of the spline pair along the proximaltransition segment and the distal transition segment.

The first spline and a second spline of the plurality of splines mayform a first spline pair. The second spline may be circumferentiallyadjacent to the first spline. The device may further comprise a secondspline pair comprising a third spline of the plurality of splines and afourth spline to the plurality of splines. The fourth spline may becircumferentially adjacent to the third spline. Each spline of a splinepair may be parallel to the other spline of the spline pair along theintermediate segment. Each spline of a spline pair may be parallel tothe other spline of the spline pair along the proximal segment and thedistal segment. The intermediate segments of each spline pair may bespaced further apart from each other than the proximal segments and thedistal segments.

A least one spline of the plurality of splines may be devoid ofelectrodes.

The expandable structure may comprise a longitudinal axis between theproximal hub and the distal hub. The proximal segments of each of thesplines of the plurality of splines may radially diverge away from thelongitudinal axis and the distal segments of each of the splines of theplurality of splines may radially converge towards the longitudinalaxis.

The plurality of splines may be configured to extend outwardly on oneside of a plane crossing a longitudinal axis of the expandablestructure. Splines of the plurality of splines comprising electrodes maybe configured to extend outwardly on one side of a plane crossing alongitudinal axis of the expandable structure. The splines of theplurality of splines comprising electrodes may circumferentially occupy100° to 120°. Splines of the plurality of splines not comprisingelectrodes may be configured to extend outwardly on a second side of theplane crossing the longitudinal axis of the expandable structure. Thesecond side may be opposite the one side.

The outer tube may comprise a proximal portion and a distal portion. Theproximal portion may have a higher durometer than the distal portion.The outer tube may comprise a plurality of longitudinal portions along alength of the outer tube. Each longitudinal portion the plurality oflongitudinal portions may have a higher durometer than the longitudinalportions of the plurality of longitudinal portions distal thereto. Atleast one longitudinal portion of the plurality of longitudinal portionsmay be configured with a length and durometer for positioning the atleast one longitudinal portion in a specific anatomy. The specificanatomy may comprise a chamber of a heart. The specific anatomy maycomprise a blood vessel. The blood vessel may comprise the rightpulmonary artery.

The outer tube may comprise a first outer diameter at the proximal endof the outer tube and a second outer diameter at the distal end of theouter tube. The first outer diameter may be greater than the secondouter diameter.

A proximal portion of the outer tube may comprise a first plurality oflayers. A distal portion of the outer tube may comprise a secondplurality of layers. The first plurality of layers may comprise morelayers than the second plurality of layers.

The outer tube may comprise a hinge joined to the proximal hub. Thehinge may be configured to resist kinking upon bending of the devicetransverse to a longitudinal axis of the outer tube. The hinge maycomprise a coil comprising a proximal end and a distal end. The proximalend of the coil may surround a portion of the tubing and the distal endof the coil may surround a portion of the proximal hub. The hinge maycomprise a first wire comprising a helical winding, a second wirecomprising a helical winding and occupying spaces between helices of thefirst wire, and a third wire comprising a helical winding and occupyingspaces between helices the first wire and between helices of the secondwire.

The outer tube may comprise tubing. The tubing may comprise an innerdiameter configured to mate with an outer diameter of the proximal hub.The tubing may be configured to abut a proximal end of the proximal hub.The tubing may form a fluid seal between the outer tube and the proximalhub.

The first spline may comprise a spline tube. The first electrode may beon an outer surface of the spline tube.

The device may further comprise a spline tube at least partiallycovering two circumferentially adjacent splines of the plurality ofsplines. The spline tube may be configured to inhibit the twocircumferentially adjacent splines from rotating relative to oneanother. The spline tube may diverge into two spatially separatedtubular channels along the intermediate segments of the twocircumferentially adjacent splines.

Circumferentially adjacent splines of the plurality of splines may begrouped into spline pairs. Each of the spline pairs may comprise aproximal tubing at least partially covering the proximal segments and adistal tubing at least partially covering the distal segments. Theproximal tubings and the distal tubings may be configured to inhibit thesplines of each of the spline pairs from rotating relative to oneanother. Each of the proximal tubings and the distal tubings maycomprise heat-shrink tubing.

Circumferentially adjacent splines of the plurality of splines may ebgrouped into spline pairs. Each of the spline pairs may comprise a wirebent at a proximal end and having wire ends terminating at a distal end.

The proximal hub may comprise a proximal end, a distal end, and acentral lumen extending from the proximal end of the proximal hub to thedistal end of the proximal hub. The shaft may slidably extend throughthe central lumen of the proximal hub. The device may further comprise aplurality of peripheral lumens radially outward of the central lumen ofthe proximal hub. The plurality of peripheral lumens may be configuredto transfer fluid flowing through the outer tube to the distal end ofthe proximal hub. At least one peripheral lumen of the plurality ofperipheral lumens may be configured to receive an electrical conductorextending from the handle to the first electrode. The device may furthercomprise a plurality of spline channels extending proximally from thedistal end of the proximal hub into a distal portion of the proximalhub. One spline of the plurality of splines may be in each splinechannel of the plurality of spline channels of the proximal hub. Theplurality of spline channels may extend through the distal portion ofthe proximal hub. Circumferentially adjacent splines of the plurality ofsplines may be grouped into spline pairs. Each of the spline pairs maycomprise a wire bent at a proximal end. The proximal hub may comprise aplurality of recesses proximal to the distal portion of the proximalhub. The bent proximal ends of the wire of each of the spline pairs maybe in a recess of the plurality of recesses. The plurality of recessesmay be configured to inhibit movement of the plurality of splinesproximal to the recesses.

The distal hub may comprise a proximal end, a distal end, and a centrallumen extending from the proximal end of the distal hub to the distalend of the distal hub. The shaft may be fixably coupled to the centrallumen of the distal hub. The device may further comprise a plurality ofspline channels extending distally from the proximal end of the distalhub into the distal hub. One spline of the plurality of splines may bein each spline channel of the plurality of spline channels of the distalhub. Each spline channel of the plurality of spline channels of thedistal hub may terminate proximal to the distal end of the distal hub.The proximal end of the distal hub may comprise a tapered surface. Thetapered surface of the proximal end of the distal hub may compriseopenings to the plurality of spline channels. The tapered surfaceproximal end of the distal hub may be configured to facilitate bendingof the splines in a radially outward direction. The distal end of thedistal hub may comprise an atraumatic configuration.

The handle may comprise a handle base comprising a proximal end, adistal end, and a lumen extending from the proximal end to the distalend. The handle may further comprise a proximal end of the outer tubecoupled to the lumen of the handle base. The shaft may slidably extendthrough the lumen of the handle base. The handle may further comprise anactuator affixed to a proximal end of the shaft. The actuator may bemoveable relative to the handle base in a proximal direction and in adistal direction. The actuator may be configured to expand theexpandable structure when moved in a distal direction and to compressthe expandable structure when moved in a proximal direction. The handlemay further comprise an outer handle extending from the handle base, asecuring member comprising a proximal end affixed to the actuator, and alocking member positioned along the securing member between the outerhandle and the actuator. The locking member may be configured to bemoved along the longitudinal axis of the securing member and secured ata position along a length of the securing member to inhibit movement ofthe actuator in a distal direction.

The securing member may comprise a threaded shaft and the locking membermay comprise a threaded channel. The locking member may belongitudinally moveable along the securing member by rotating thelocking member around the threaded shaft.

The handle may further comprise a locking member having a lockedconfiguration and an unlocked configuration. The locking member maycomprise a main body comprising a proximal end and a distal end, achannel extending from the proximal end to the distal end, and aprotrusion extending into the channel of the locking member. Theactuator may extend through the channel of the locking member. Theprotrusion may be configured to inhibit the actuator from moving in atleast one of a proximal direction and a distal direction relative to thehandle base when the locking member may be in the locked configuration.The actuator may be moveable in the proximal direction and in the distaldirection when the locking member may be in the unlocked configuration.The actuator may comprise an elongate body, a textured surface along alength of the elongate body of the actuator, and the locking membermoveable between the locked configuration and the unlocked configurationby rotating the locking member around the elongate body of the actuator.The protrusion may be configured to interface with the textured surfacein a locked position and configured to not interface with the texturedsurface in the unlocked position.

The locking member may further comprise a tab extending away from themain body. The tab may be positionable in a first position relative tothe handle base when the locking member is in a locked configuration.The tab may be positionable in a second position when the locking memberis in an unlocked configuration. The textured surface may comprise aseries of ridges. The protrusion of the locking member may be configuredto mate with a notch between the ridges. The channel of the lockingmember may be oblong. The locking member may be configured to switchbetween a locked configuration and an unlocked configuration by rotatingthe locking member a quarter turn.

The handle base further may comprise an aperture in a sidewall extendinginto the lumen of the handle base and proximal to the proximal end ofthe outer tube. An electrical conductor may extend from an electricalsocket into the outer tube through the aperture of the handle base.

The shaft may comprise a lumen. The lumen of the shaft may be configuredto receive a guidewire. A proximal end of the shaft may be configured toreceive fluid. The proximal end of the shaft may be joined to a fluidvalve. The shaft may comprise a sidewall and an aperture in thesidewall. The aperture may be configured to permit fluid to flow out ofthe lumen of the shaft and to the proximal hub.

The device may be configured to transfer fluid injected into the shaftthrough the shaft to the distal hub and through the outer tube to theproximal hub. The shaft may comprise a plurality of hypotubes. Theplurality of hypotubes may comprise a first hypotube having a proximalend and a distal end, and a second hypotube having a proximal end and adistal end. The distal end of the first hypotube may be in the proximalend of the second hypotube. The proximal end of the second hypotube maybe in the distal end of the first hypotube. The plurality of hypotubesmay include three hypotubes. At least one hypotube of the plurality ofhypotubes may comprise a proximal portion having a first outer diameterand a distal portion having a second outer diameter less than the firstouter diameter. At least one hypotube of the plurality of hypotubes maycomprise a sidewall and an aperture through the sidewall.

The device may further comprise an inflatable member. The device mayfurther comprise an inflation lumen in fluid communication with theinflatable member.

In some examples, a device comprises, or alternatively consistsessentially of, a handle and an expandable structure. The expandablestructure has a collapsed state and a self-expanded state. Theexpandable structure comprises a plurality of splines extending from aproximal hub to a distal hub. The device further comprises an energydelivery neuromodulator on a first spline of the plurality of splines,an outer tube extending from the handle to the proximal hub, and a shaftextending through the outer tube from the handle to the distal hub, thehandle configured to retract the shaft. The energy deliveryneuromodulator may comprise an electrode. The neuromodulator maycomprise a transducer.

In some examples, a device comprises, or alternatively consistsessentially of, a handle and an expandable structure. The expandablestructure has a collapsed state and a self-expanded state. Theexpandable structure comprises a plurality of splines extending from aproximal hub to a distal hub. The device further comprises aneuromodulator on a first spline of the plurality of splines, an outertube extending from the handle to the proximal hub, and a shaftextending through the outer tube from the handle to the distal hub. Thehandle is configured to retract the shaft. The neuromodulator maycomprise a radiofrequency electrode, an ultrasound element, a laserelement, a microwave element, a cryogenic element, a thermal deliverydevice, or a drug delivery device.

Use of the device may be for neuromodulation. Use of the device may befor treatment of a cardiovascular condition. Use of the device may befor treatment of acute heart failure. Use of the device may be fortreatment of shock. Use of the device may be for treatment of valvulardisease. Use of the device may be for treatment of angina. Use of thedevice may be for treatment of microvascular ischemia. Use of the devicemay be for treatment of myocardial contractility disorder. Use of thedevice may be for treatment of cardiomyopathy. Use of the device may befor treatment of hypertension. Use of the device may be for treatment ofpulmonary hypertension. Use of the device may be for treatment ofsystemic hypertension. Use of the device may be for treatment oforthostatic hypertension. Use of the device may be for treatment oforthopnea. Use of the device may be for treatment of dyspenea. Use ofthe device may be for treatment of dysautonomia. Use of the device maybe for treatment of syncope. Use of the device may be for treatment ofvasovagal reflex. Use of the device may be for treatment of carotidsinus hypersensitivity. Use of the device may be for treatment ofpericardial effusion. Use of the device may be for treatment of cardiacstructural abnormalities.

In some examples, a method of modulating a nerve comprises, oralternatively consists essentially of, inserting a distal portion of thedevice into vasculature, allowing the expandable member to self-expand,actuating the handle to further expand the expandable structure toanchor the expandable structure in the vasculature, and activating thefirst electrode to stimulate the nerve.

The method may further comprise accessing the vasculature with a needleand a syringe. Accessing the vasculature may be at a jugular vein.Accessing the vasculature may be at a left jugular vein.

The method may further comprise inserting a guidewire into thevasculature. The shaft may comprise a lumen extending from a proximalportion of the device to the distal portion of the device. Inserting thedistal portion of the device into the vasculature may comprise trackingthe device over the guidewire to position the expandable structure at atarget location in the vasculature. The guidewire may slide through thelumen of the shaft.

The method may further comprise inserting a Swan-Ganz cathetercomprising a distal end comprising a balloon into vasculature, inflatingthe balloon, allowing the balloon to be carried by blood flow to thetarget location, inserting the guidewire through a lumen in theSwan-Ganz catheter, deflating the balloon, and retracting the Swan-Ganzcatheter from the vasculature.

The target location may be a pulmonary artery. The target location maybe a right pulmonary artery. The target location may be a pulmonarytrunk. The target location may be a left pulmonary artery.

The method may further comprise inserting an introducer in thevasculature. Inserting the distal portion of the device into thevasculature may comprise inserting the device through a sheath of theintroducer. The method may further comprise at least one of proximallyretracting a distal end of the introducer sheath and distally advancingthe distal portion of the device, allowing the expandable structure toself-expand. The method may further comprise actuating a locking memberon the handle.

The nerve may comprise a cardiopulmonary nerve. The nerve may comprise aright dorsal medial CPN. The nerve may comprise a right dorsal lateralCPN. The nerve may comprise a right stellate CPN. The nerve may comprisea right vagal nerve or vagus. The nerve may comprise a right cranialvagal CPN. The nerve may comprise a right caudal vagal CPN. The nervemay comprise a right coronary cardiac nerve. The nerve may comprise aleft coronary cardiac nerve. The nerve may comprise a left lateralcardiac nerve. The nerve may comprise a left recurrent laryngeal nerve.The nerve may comprise a left vagal nerve or vagus. The nerve maycomprise a left stellate CPN. The nerve may comprise a left dorsallateral CPN. The nerve may comprise a left dorsal medial CPN.

The method may comprise positioning the expandable structure againsttissue in the vasculature so that the nerve is between the firstelectrode and a second electrode.

Activating the first electrode may comprise applying a voltage pulsehaving a first polarity. The method may further comprise, beforeactivating the first electrode, applying a pre-pulse of voltage totissue surrounding the nerve. The pre-pulse may have a second polarityopposite the first polarity.

The method may further comprise measuring pressure in a right ventricleand approximating pressure in the left ventricle from the pressuremeasured in the right ventricle.

The method may further comprise positioning a return conductor in thevasculature. The return conductor may be configured to conduct currentfrom an activated electrode.

A current vector from the first electrode to the return electrode may beaway from at least one of a heart and a trachea. Positioning the returnconductor in the vasculature may comprise positioning the returnelectrode at least 5 mm away from the first electrode. Positioning thereturn conductor in the vasculature may comprise positioning the returnelectrode in a right ventricle. Positioning the return conductor in thevasculature may comprise positioning the return electrode a superiorvena cava. Positioning the return conductor in the vasculature maycomprise positioning the return electrode a brachiocephalic vein.

In some examples, a device for increasing heart contractility maycomprise, or alternatively consists essentially of, an expandablestructure and a plurality of electrodes. The expandable structure has acollapsed state and an expanded state. The expandable structure includesan inflatable structure. The expandable structure may be configured forplacement in a pulmonary artery. The expandable structure may beconfigured for delivery of energy from at least one electrode of theplurality of electrodes to increase heart contractility.

The inflatable structure may comprise at least one electrode of theplurality of electrodes. The inflatable structure may comprise a firstinflatable element and a second inflatable element. The first inflatableelement may comprise a first balloon. The first balloon of the firstinflatable element may comprise at least one electrode of the pluralityof electrodes. The first balloon of the first inflatable element maycomprise at least two electrodes of the plurality of electrodes. The atleast two electrodes may be circumferentially spaced on the firstballoon. The first inflatable element may comprise a second balloon. Thesecond balloon of the first inflatable element may comprise at least oneelectrode of the plurality of electrodes. The second balloon of thefirst inflatable element may comprise at least two electrodes of theplurality of electrodes. The at least two electrodes may becircumferentially spaced on the second balloon. The first inflatableelement may comprise a valley between the first balloon and the secondballoon. The valley may comprise at least one electrode of the pluralityof electrodes. The second inflatable element may comprise a firstballoon. The first balloon of the second inflatable element may compriseat least one electrode of the plurality of electrodes. The first balloonof the second inflatable element may comprise at least two electrodes ofthe plurality of electrodes. The at least two electrodes may becircumferentially spaced on the first balloon. The second inflatableelement may comprise a second balloon. The second balloon of the firstinflatable element may comprise at least one electrode of the pluralityof electrodes. The second balloon of the first inflatable element maycomprise at least two electrodes of the plurality of electrodes. The atleast two electrodes may be circumferentially spaced on the secondballoon. The second inflatable element may comprise a valley between thefirst balloon and the second balloon. The valley may comprise at leastone electrode of the plurality of electrodes. The first inflatableelement may comprise a balloon. The second inflatable element maycomprise a balloon. The third inflatable element may comprise a balloon.The fourth inflatable element may comprise a balloon. The firstinflatable element may comprise a balloon. The second inflatable elementmay comprise a balloon. The third inflatable element may comprise aballoon. The fourth inflatable element may comprise a balloon. The firstinflatable element may be circumferentially spaced from the secondinflatable element by 90°. The second inflatable element may becircumferentially spaced from the third inflatable element by 90°. Thethird inflatable element may be circumferentially spaced from the fourthinflatable element by 90°. The fourth inflatable element may becircumferentially spaced from the first inflatable element by 90°. Theinflatable structure may comprise a fifth inflatable element and a sixthinflatable element. The inflatable element may comprise a balloon. Thesecond inflatable element may comprise a balloon. The third inflatableelement may comprise a balloon. The fourth inflatable element maycomprise a balloon. The fifth inflatable element may comprise a balloon.The sixth inflatable element may comprise a balloon. The firstinflatable element may be circumferentially spaced from the secondinflatable element by 60°. The second inflatable element may becircumferentially spaced from the third inflatable element by 60°. Thethird inflatable element may be circumferentially spaced from the fourthinflatable element by 60°. The fourth inflatable element may becircumferentially spaced from the fifth inflatable element by 60°. Thefifth inflatable element may be circumferentially spaced from the sixthinflatable element by 60°. The sixth inflatable element may becircumferentially spaced from the first inflatable element by 60°. Theinflatable elements may comprise lumens. The lumens may extend in adirection parallel to a longitudinal axis of the device. The expandablestructure may comprise a plurality of struts. The plurality of strutsmay comprise at least one electrode of the plurality of electrodes. Atleast one strut of the plurality of struts may be circumferentiallybetween a first edge of the first inflatable element and a second edgeof the second inflatable element. At least one other strut of theplurality of struts may be circumferentially between a second edge ofthe first inflatable element and a first edge of the second inflatableelement. The at least one strut may comprise the at least one electrode.The at least one other strut may not comprise an electrode. In severalexamples, no strut of the plurality of struts is circumferentiallybetween a second edge of the first inflatable element and a first edgeof the second inflatable element. The device may further comprise aguidewire lumen. The device may further comprise a Swan-Ganz balloon. Atleast one electrode of the plurality of electrodes may be laser ablatedto increase surface area. At least two electrodes of the plurality ofelectrodes are overmolded to form an electrode assembly. The device mayfurther comprise a first pressure sensor. The first pressure maycomprise a MEMS sensor. The first pressure sensor may be configured forplacement in a pulmonary artery. The device may further comprise asecond pressure sensor. The second pressure may comprise a MEMS sensor.The second pressure sensor may be configured for placement in a rightventricle.

In some examples, a device for increasing heart contractility maycomprise, or alternatively consists essentially of, an expandablestructure. The expandable structure has a collapsed state and anexpanded state. The expandable structure comprises a plurality ofstruts, an open distal end in the expanded state, and a plurality ofelectrodes. The expandable structure may be configured for placement ina pulmonary artery. The expandable structure may be configured for Theexpandable structure may be configured for delivery of energy from atleast one electrode of the plurality of electrodes to increase heartcontractility. At least two struts of the plurality of struts may belinked at a first point at a proximal end of the expandable structure.At least two other struts of the plurality of struts may be linked at asecond point at the proximal end of the expandable structure. The devicemay further comprise a first tether coupled to the first point. Thedevice may further comprise a second tether coupled to the second point.Upon proximal retraction of the first tether and the second tethertowards a catheter, the expandable structure may be configured to changefrom the expanded state to the collapsed state. At least one of thefirst tether and the second tether may comprise bundled electricalconnectors electrically coupled to the plurality of electrodes. At leasttwo struts of the plurality of struts may comprise the plurality ofelectrodes. A first strut of the at least two struts may comprise afirst electrode assembly comprising at least two electrodes of theplurality of electrodes. A second strut of the at least two struts maycomprise a second electrode assembly comprising at least two electrodesof the plurality of electrodes. A first strut of the at least two strutsmay comprise at least two electrodes of the plurality of electrodes.Each of the at least two electrodes may be independently coupled to thefirst strut. The at least two electrodes may be longitudinally spaced. Asecond strut of the at least two struts may comprise at least twoelectrodes of the plurality of electrodes. Each of the at least twoelectrodes may be independently coupled to the second strut. The atleast two electrodes may be longitudinally spaced. The at least twostruts of the first strut and the at least two struts of the secondstrut may be configured to nest when the expandable structure is in thecollapsed state. At least four struts of the plurality of strutscomprise the plurality of electrodes. A first strut of the at least fourstruts may comprise a first electrode assembly comprising at least twoelectrodes of the plurality of electrodes. A second strut of the atleast four struts may comprise a second electrode assembly comprising atleast two electrodes of the plurality of electrodes. A third strut ofthe at least four struts may comprise a second electrode assemblycomprising at least two electrodes of the plurality of electrodes. Afourth strut of the at least four struts may comprise a second electrodeassembly comprising at least two electrodes of the plurality ofelectrodes. A first strut of the at least four struts may comprise atleast two electrodes of the plurality of electrodes. Each of the atleast two electrodes may be independently coupled to the first strut.The at least two electrodes may be longitudinally spaced. A second strutof the at least four struts may comprise at least two electrodes of theplurality of electrodes. Each of the at least two electrodes may beindependently coupled to the second strut. The at least two electrodesmay be longitudinally spaced. A third strut of the at least four strutsmay comprise at least two electrodes of the plurality of electrodes.Each of the at least two electrodes may be independently coupled to thethird strut. The at least two electrodes may be longitudinally spaced. Afourth strut of the at least four struts may comprise at least twoelectrodes of the plurality of electrodes. Each of the at least twoelectrodes may be independently coupled to the fourth strut. The atleast two electrodes may be longitudinally spaced. The at least twoelectrodes of the first strut, the at least two electrodes of the secondstrut, the at least two electrodes of the third strut, and the at leasttwo electrodes of the fourth strut are configured to nest when theexpandable structure may be in the collapsed state. The expandablestructure may comprise a closed proximal end in the expanded state. Theexpandable structure may comprise additional struts distal to theplurality of struts. The expandable structure may comprise additionalstruts proximal to the plurality of struts. The plurality of electrodesmay be on struts of the plurality of struts on a first side of planecrossing a longitudinal axis of the expandable structure. In severalexamples, a second side of the plane does not include electrodes. Inseveral examples, a second side of the plane does not include struts forthe longitudinal length of the plurality of electrodes.

The device may further comprise a guidewire sheath on a side of theexpandable structure. The plurality of struts may taper proximally tothe guidewire sheath. The plurality of struts may comprise six struts.Four struts may comprise the plurality of electrodes. Two struts may befree of the plurality of electrodes. In the expanded state, the fourstruts may be on a first side of a plane bisecting the expandablestructure. The two struts may be on an opposite side of the plane.Proximal ends of the plurality of struts may be coupled to a hub. Theexpandable structure may comprise a proximal portion comprising theplurality of electrodes and a distal portion comprising the open distalend in the expanded state. The proximal portion and the distal portionmay be monolithic. The proximal portion may be coupled to the distalportion. The proximal portion may have a first radial stiffness. Thedistal portion may have a second radial stiffness greater than the firstradial stiffness. In the expanded state, the proximal portion may have afirst diameter. The distal portion may have a second diameter less thanthe first diameter. The first diameter may be 2 mm to 8 mm greater thanthe second diameter. The proximal portion may comprise bifurcatedstruts. The proximal portion may comprise S-shaped features at proximalends of the plurality of struts.

The expandable structure may comprise a guidewire sheath comprising atleast some electrodes of the plurality of electrodes. The guidewiresheath may have a distal end coupled to the distal portion. Theguidewire sheath may be configured to bow radially outward in responseto distal advancement of the guidewire sheath. The device may furthercomprise a spline comprising at least some other electrodes of theplurality of electrodes. The spline may have a distal end coupled to thedistal portion. The spline may be configured to bow radially outward inresponse to distal advancement of the spline.

In some examples, a device for increasing heart contractility maycomprise, or alternatively consists essentially of, an expandablestructure. The expandable structure has a collapsed state and anexpanded state. The expandable structure comprises a first wire, asecond wire, and a guidewire sheath. The guidewire sheath comprises aplurality of electrodes. The guidewire sheath is configured to bowradially outward in response to distal advancement of the guidewiresheath. Distal ends of the first wire, the second wire, and theguidewire sheath coupled together. The expandable structure isconfigured for placement in a pulmonary artery. Delivery of energy fromat least one electrode of the plurality of electrodes is configured toincrease heart contractility.

The device may further comprise a spline comprising a second pluralityof electrodes. The spline may have a distal end coupled to the distalends of the first wire, the second wire, and the guidewire sheath. Thespline may be configured to bow radially outward in response to distaladvancement of the spline. The guidewire sheath and the spline may beconfigured to be independently operated. The guidewire sheath and thespline may be configured to be dependently operated. The guidewiresheath and the spline may be configured to be nested in an advancedstate. In some examples, a method of positioning the device comprise, oralternatively consists essentially of, advancing the expandablestructure into a left pulmonary artery in the collapsed state andexpanding the expandable structure to the expanded state. The first wiremay be preloaded against a first sidewall of the left pulmonary artery.The second wire may be preloaded against an opposite wall of the leftpulmonary artery. The method may further comprise proximally retractingthe expandable structure in the expanded state. During retraction, thesecond wire may snap into an ostium of a right pulmonary artery. Themethod may further comprise distally advancing the guidewire sheath. Theguidewire sheath may bow radially outward into the right pulmonaryartery.

In some examples, a method of detecting catheter movement comprises, oralternatively consists essentially of, positioning a first sensor in afirst body cavity, monitoring a first parameter profile of the firstbody cavity, positioning a second sensor in a second body cavity,monitoring a second parameter profile of the second body cavity, andwhen the second parameter profile is the same as the first parameterprofile at a second time after the first time, taking a cathetermovement action. The second parameter profile is different than thefirst parameter profile at a first time. In several embodiments, amethod of detecting catheter movement is non-therapeutic and need not beperformed by a physician.

The first sensor may comprise a first pressure sensor. The firstpressure sensor may comprise a MEMS sensor. The first parameter profilemay comprise a pressure range. The second sensor may comprise a secondpressure sensor. The second pressure sensor may comprise a MEMS sensor.The second parameter profile may comprise a pressure range. The firstbody cavity may comprise a pulmonary artery and the second body cavitymay comprise a right ventricle. The first body cavity may comprise aright ventricle and the second body cavity may comprise a right atrium.The first body cavity may comprise a right atrium and the second bodycavity may comprise a vena cava. The catheter movement action maycomprise sounding an alarm. The catheter movement action may comprisestopping neurostimulation. The catheter movement action may comprisecollapsing an expandable element. The catheter movement action maycomprise sending a wireless message.

In some examples, a system for detecting movement of a cathetercomprises, or alternatively consists essentially of, a first sensorconfigured to be positioned in a first body cavity and to monitor afirst parameter profile of the first body cavity and a second sensorconfigured to be positioned in a second body cavity and to monitor asecond parameter profile of the second body cavity. The second parameterprofile is different than the first parameter profile at a first time.The second parameter profile being the same as the first parameterprofile at a second time after the first time indicates movement of thecatheter.

The first sensor may comprise a first pressure sensor. The firstpressure sensor may comprise a MEMS sensor. The first parameter profilemay comprise a pressure range. The second sensor may comprise a secondpressure sensor. The second pressure sensor may comprise a MEMS sensor.The second parameter profile may comprise a pressure range. The systemmay further comprise the catheter. The catheter may comprise the firstsensor and the second sensor. The second sensor may be proximal to thefirst sensor.

In some examples, a method of detecting catheter movement comprises, oralternatively consists essentially of, positioning a sensor in a rightventricle and monitoring a parameter profile of the right ventricle fora change greater than a threshold value. In several embodiments, when achange greater than a threshold value occurs, a notification is sent toindicate, for example, that the catheter has moved. This notificationcan be an alarm (including a wireless message, an auditory alarm, etc.),an automated function, etc.

The threshold value may be indicative of movement of the sensor againsta tricuspid valve. The threshold value may be indicative of movement ofthe sensor proximal to a tricuspid valve. The parameter may comprisepressure. The sensor may comprise a MEMS sensor. The method may furthercomprise detecting the change greater than the threshold value andtaking a catheter movement action. The catheter movement action maycomprise sounding an alarm. The catheter movement action may comprisestopping neurostimulation. The catheter movement action may comprisecollapsing an expandable element. A catheter may comprise the sensor.The catheter movement action may comprise sending a wireless message.Positioning the sensor in the right ventricle may comprise providingslack to the catheter. Upon proximal retraction of the catheter, thecatheter may be made taut and/or the sensor may be moved towards anannulus of a tricuspid valve.

In some examples, a method of detecting catheter movement comprises, oralternatively consists essentially of, positioning a sensor in a heartchamber and monitoring a parameter profile of the heart chamber for achange greater than a threshold value.

In some examples, a method of detecting catheter movement comprises, oralternatively consists essentially of, positioning a sensor in avascular cavity and monitoring a parameter profile of the vascularcavity for a change greater than a threshold value.

In some examples, a method of detecting catheter movement comprises, oralternatively consists essentially of, positioning a sensor in a bodycavity and monitoring a parameter profile of the body cavity for achange greater than a threshold value.

In some examples, a system for detecting movement of a cathetercomprises, or alternatively consists essentially of, a sensor configuredto be positioned in a right ventricle and to monitor a parameter profileof the right ventricle. A change in the parameter profile greater than athreshold value indicates movement of the catheter.

The threshold value may be indicative of movement of the sensor againsta tricuspid valve. The threshold value may be indicative of movement ofthe sensor proximal to a tricuspid valve. The parameter may comprisepressure. The sensor may comprise a MEMS sensor. The system may furthercomprise the catheter. The catheter may comprise the sensor.

In some examples, a method of setting a stimulation vector comprises, oralternatively consists essentially of, setting a first electrode as acathode and setting a second electrode as an anode. A line between thefirst electrode and the second electrode is a first stimulation vector.The method further comprises setting a third electrode as an anode. Aline between the first electrode and the third electrode is a secondstimulation vector. The method further comprises selecting as thestimulation vector one of the first stimulation vector or the secondstimulation vector that is most orthogonal to a primaryelectrocardiogram (ECG) vector between a first ECG lead and a second ECGlead.

The selected stimulation vector may reduce a quantity of stimulationnoise interference on an ECG signal. The first ECG lead and the secondECG lead may be coupled to an implantable cardiac defibrillator. Themethod may further comprise establishing the first electrode as capableof capturing a nerve when used as the cathode. The method may furthercomprise setting a fourth electrode as an anode. A line between thefirst electrode and the fourth electrode may be a third stimulationvector. Selecting the stimulation vector may comprise selecting one ofthe first stimulation vector, the second stimulation vector, or thethird stimulation vector that is most orthogonal to the primary ECGvector. The method may further comprise using the stimulation vector fortherapeutic stimulation.

In some examples, a method of setting a stimulation vector comprises, oralternatively consists essentially of, setting a first electrode as acathode and setting each of a plurality of other electrodes as an anode.The plurality of other electrodes does not include the first electrode.Lines between the first electrode and each of the plurality of otherelectrodes are potential stimulation vectors. The method furthercomprises selecting as the stimulation vector the potential stimulationvector of the potential stimulation vectors that is most orthogonal to aprimary electrocardiogram (ECG) vector between a first ECG lead and asecond ECG lead.

The selected stimulation vector may reduce a quantity of stimulationnoise interference on an ECG signal. The first ECG lead and the secondECG lead may be coupled to an implantable cardiac defibrillator. Themethod may further comprise establishing the first electrode as capableof capturing a nerve when used as the cathode. The plurality of otherelectrodes may comprise between 2 electrodes and 19 electrodes. Theplurality of other electrodes may comprise between 2 electrodes and 11electrodes. The plurality of other electrodes may comprise between 2electrodes and 8 electrodes. The plurality of other electrodes may be360° around the first electrode. The method may further comprise usingthe stimulation vector for therapeutic stimulation.

In some examples, a system for blanking neurostimulation from anelectrocardiogram (ECG) comprises, or alternatively consists essentiallyof, an ECG blanker configured to communicate with an ECG systemconfigured to monitor a subject, an ECG amplifier configured to receivea signal from the ECG system, and a neurostimulation system configuredto apply stimulation to the subject. The ECG blanker is configured toinstruct the neurostimulation system to not apply neurostimulationduring a heartbeat, and during neurostimulation by the neurostimulationsystem, blanking the signal from the ECG system.

The ECG blanker may be configured to predict when the heartbeat willoccur. The ECG blanker may use deterministic timing to predict when theheartbeat will occur. Blanking the signal from the ECG system maycomprise manipulating data from the ECG system and sending themanipulated data to the ECG amplifier. Blanking the signal from the ECGsystem may comprise holding the ECG signal at constant voltage duringstimulation pulses. The neurostimulation system may comprise the ECGblanker.

In some examples, method of modifying an electrocardiogram (ECG)waveform comprises, or alternatively consists essentially of, detectingR waves of ECGs for a first duration, measuring R to R intervals of theECGs for the first duration, computing a weighted sum average of the Rto R intervals, predicting a window for a next heartbeat using theweighted sum average, and blanking neurostimulation from occurringduring the predicted window.

Computing the weighted sum average may comprise excluding outliers. Themethod may comprise computing the weighted sum average based on a secondduration. The second duration may overlap the first duration. Blankingthe neurostimulation may comprise allowing the neurostimulation betweenan expected T wave and an expected Q wave. Blanking the neurostimulationmay comprise allowing the neurostimulation between an expected S waveand an expected Q wave. Blanking the neurostimulation may compriseallowing the neurostimulation between an expected S wave and an expectedP wave. Blanking the neurostimulation may comprise setting a blankingperiod using the predicted window. The blanking period may comprise 300ms after a predicted R wave. The blanking period may comprise 700 msafter a predicted R wave. The blanking period may comprise 300 ms beforea next predicted R wave. The blanking period may comprise 700 ms beforea next predicted R wave. The blanking period may comprise 30% of thepredicted window after a predicted R wave. The blanking period maycomprise 70% of the predicted window after a predicted R wave. Theblanking period may comprise 30% of the predicted window before a nextpredicted R wave. The blanking period may comprise 70% of the predictedwindow before a next predicted R wave.

In some examples, a system for filtering noise from an electrocardiogram(ECG) comprises, or alternatively consists essentially of, a filterassembly configured to communicate with ECG leads configured to monitora subject, an ECG system configured to receive a signal from the ECGleads, and a neurostimulation system configured to apply stimulation tothe subject. The filter assembly is configured to produce anoise-filtered signal including the signal from the ECG leads minusnoise from the neurostimulation system and send the noise-filteredsignal to the ECG system.

The filter assembly may comprise an ECG input configured to be coupledto the ECG leads, an ECG output configured to be coupled to the ECGsystem, and a filter communicatively between the ECG input and the ECGoutput. The filter may comprise a low pass filter. The filter maycomprise a cutoff frequency less than a neurostimulation frequency. Thefilter may comprise a notch filter. The filter may be adjustable to afrequency. The neuromodulation system may be configured to set thefrequency. The filter assembly may include an input for manually orelectronically setting the frequency. The frequency may be 20 Hz. Thefrequency may be 10 Hz. The ECG output may comprise wires mimicking ECGleads. The filter assembly may further comprise an analog to digitalconverter communicatively between the ECG input and the ECG output and adigital to analog converter communicatively between the filter and theECG output. The neurostimulation system may comprise the filterassembly.

In some examples, a neuromodulation system for matching aneurostimulation frequency to an electrocardiogram (ECG) monitoringfrequency comprises, or alternatively consists essentially of, an inputconfigured to receive an ECG system operating frequency and aneurostimulation frequency adjustable to match the ECG system operatingfrequency.

The ECG system operating frequency may be 50 Hz. The ECG systemoperating frequency may be 60 Hz. The system may be configured to adjustat least one stimulation parameter. The at least one stimulationparameter may comprise amplitude, pulse width, duty cycle, or waveform.The system may be configured to determine a therapeutic frequency.Adjustment of the at least one stimulation parameter may approximatesneurostimulation at the therapeutic frequency.

In some examples, an electrode assembly comprises, or alternativelyconsists essentially of, a portion of a strut including a first side, asecond side opposite the first side, and a thickness between the firstside and the second side, an aperture in the portion of the strut,electrically-insulating material over the first side of the strut andover the second side of the strut, an electrode inserted through thefirst side of the strut and prolapsed from the second side of the strut,and a conductor electrically coupled to the electrode. The electrodecomprises a swaged portion on the first side of the strut.

The strut may be a laser-cut strut. The aperture may be laser-cut. Thefirst side of the strut may comprise a channel. The conductor may bepositioned in the channel. The assembly may further comprise theelectrically-insulating material over the swaged portion of theelectrode. The assembly may further comprise a plurality of apertures inthe portion of the strut and one electrode in each of the plurality ofapertures and comprising a swaged portion on the first side of thestrut. The assembly may further comprise a plurality of portions ofstruts each comprising at least one electrode in an aperture of onestrut and comprising a swaged portion on the first side of the onestrut.

The methods summarized above and set forth in further detail belowdescribe certain actions taken by a practitioner; however, it should beunderstood that they can also include the instruction of those actionsby another party. Thus, actions such as “positioning an electrode”include “instructing positioning of an electrode.”

For purposes of summarizing the invention and the advantages that may beachieved, certain objects and advantages are described herein. Notnecessarily all such objects or advantages need to be achieved inaccordance with any particular example. In some examples, the inventionmay be embodied or carried out in a manner that can achieve or optimizeone advantage or a group of advantages without necessarily achievingother objects or advantages.

The examples disclosed herein are intended to be within the scope of theinvention herein disclosed. These and other examples will be apparentfrom the following detailed description having reference to the attachedfigures, the invention not being limited to any particular disclosedexample(s). Optional and/or preferred features described with referenceto some examples may be combined with and incorporated into otherexamples. All references cited herein, including patents and patentapplications, are incorporated by reference in their entirety.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates a system that can be used to applyelectrical neuromodulation to one or more nerves in and around the heartof a subject.

FIG. 2A schematically illustrates a heart and surrounding areas.

FIGS. 2B-2D are schematic illustrations of a heart and surrounding areasfrom various perspectives.

FIGS. 2E and 2F are schematic illustrations of a heart and surroundingnerves.

FIGS. 2G and 2H are schematic illustrations of vasculature and anelectrode matrix.

FIG. 2I is a schematic illustration of heart vasculature and surroundingnerves.

FIG. 2J is a schematic illustration of vasculature and surroundingnerves.

FIG. 2K is another schematic illustration of a heart and surroundingnerves.

FIG. 2L illustrates an example stimulation device.

FIG. 3A is a side perspective and partial cross-sectional view of anexample of a catheter.

FIG. 3B is a distal end view of the catheter of FIG. 3A as viewed alongline 3B-3B in FIG. 3A.

FIG. 4A is a side perspective and partial cross-sectional view ofanother example of a catheter.

FIG. 4B is a distal end view of the catheter of FIG. 4A as viewed alongline 4B-4B in FIG. 4A.

FIG. 4C is a side perspective view of an example of a portion of acatheter.

FIGS. 5 and 6 illustrate examples of catheters.

FIGS. 7A and 7B illustrate examples of a pulmonary artery catheter thatcan be used with the catheters according to the present disclosure.

FIGS. 8A and 8B illustrate examples of catheters.

FIG. 8C illustrates the catheter of FIG. 8A positioned within the mainpulmonary artery.

FIG. 8D illustrates the catheter of FIG. 8B positioned within the mainpulmonary artery.

FIGS. 9 and 10 illustrate additional examples of catheters.

FIG. 11 illustrates an example of a catheter system.

FIG. 12A-12D illustrate various examples of catheters.

FIG. 13 is a perspective view of a catheter positioned in a heart of apatient.

FIGS. 14A, 14B, 15A, 15B, 16 and 17 illustrate examples of catheters.

FIGS. 18A through 18C are side partial cross-sectional and perspectiveviews of an example catheter that is suitable for performing the methodsof the present disclosure.

FIG. 18D illustrates the catheter of FIGS. 18A through 18C positioned inthe right pulmonary artery of a heart.

FIG. 19 is partial cross-sectional and perspective view of an examplecatheter positioned in a heart of a patient.

FIG. 20 is a side partial cross-sectional and perspective view of anexample first catheter and an example second catheter that are suitablefor performing the methods of the present disclosure.

FIG. 21 illustrates an example of a stimulation system for use with thecatheters or catheter systems of the present disclosure.

FIG. 22A is a perspective view of an example of a portion of a catheter.

FIG. 22B is a side elevational view of the portion of FIG. 22A.

FIG. 22C is a distal end view of the portion of FIG. 22A.

FIG. 22D is a proximal end view of the portion of FIG. 22A.

FIGS. 22E-22G are side partial cross-sectional views of an example of acatheter including the portion of FIG. 22A.

FIGS. 22H-22L are side elevational and partial cross-sectional views ofexamples of catheter deployment systems.

FIG. 22M illustrates an example part of the portion of FIG. 22A.

FIG. 23A is a perspective view of an example segment of a strut.

FIG. 23B is a transverse cross-sectional view of an example of a strut.

FIG. 23C is a transverse cross-sectional view of an example of a strut.

FIG. 23D is a transverse cross-sectional view of another example of astrut.

FIG. 23E is a transverse cross-sectional view of yet another example ofa strut.

FIG. 23F is a transverse cross-sectional view of still another exampleof a strut.

FIG. 23G is a top partial cross-sectional view of an example segment ofa strut.

FIG. 23H illustrates an example of a strut system.

FIG. 23I shows an example in which a distance between a first strut anda second strut is less than a distance a between a third strut and thesecond strut.

FIG. 23J shows an example in which a distance between a first strut anda second strut is substantially the same as a distance a between a thirdstrut and the second strut.

FIG. 23K illustrates an example of an electrode on wire system.

FIG. 23L is a cross-sectional view of an electrode spaced from a vesselwall.

FIG. 23M shows an example electrode matrix.

FIGS. 23Ni-23Nix illustrate an example method of manufacturingcomponents on a substrate.

FIG. 24A illustrates an example of a fixation system.

FIGS. 24B and 24C illustrate the fixation system of FIG. 24A interactingwith a catheter.

FIG. 25A is a perspective view of another example of a fixation system.

FIG. 25B is a side elevational view of the fixation system of FIG. 25A.

FIG. 25C is an end view of the fixation system of FIG. 25A.

FIGS. 25D and 25E illustrate the fixation system of FIG. 25A interactingwith a catheter.

FIGS. 25F illustrates an example of a catheter comprising a shapedlumen.

FIGS. 25G-25J illustrate an example deployment out of the lumen of thecatheter of FIG. 25F.

FIG. 26A is a side elevational view of an example of a catheter system2600.

FIGS. 26B-26H illustrate an example method of deploying the cathetersystem 2600 of FIG. 26A.

FIG. 27A is a perspective view of another example of a fixation system.

FIG. 27B is an elevational view of a portion of the fixation system ofFIG. 27A.

FIGS. 27C-27F illustrate the fixation system of FIG. 27A being retractedafter engagement with tissue.

FIG. 27G is a perspective view of yet another example of a fixationsystem.

FIG. 27H is a side view of the fixation system of FIG. 27G.

FIG. 27I is a side view of still another example of a fixation system.

FIG. 28A is a side view of an example of a fixation system.

FIG. 28B is an expanded view of the dashed circle 28B in FIG. 28A.

FIG. 28C is an expanded view of the dotted square 28C in FIG. 28A.

FIG. 28D shows an example of a radiopaque marker coupled to a proximalfixation mechanism.

FIG. 28E shows an example of a hole in a proximal fixation mechanism.

FIG. 28F is a flattened view of an example of a hypotube cut pattern.

FIG. 28G is an expanded view of the dashed square 28G in FIG. 28F.

FIG. 28H is a side view of the strut of FIG. 28G.

FIG. 28I is a side view of a proximal fixation mechanism being bentradially outward.

FIG. 28J is a side view of a proximal fixation mechanism being bentradially outward and a strut being bent at a bend point.

FIG. 28K is a side view of a strut being bent at a bend point.

FIGS. 28L-28O show proximal fixation mechanisms rotating inwardly duringretrieval into a catheter.

FIG. 29A illustrates an example of a catheter system.

FIGS. 29B-29F illustrate an example method of deploying the cathetersystem of FIG. 29A.

FIG. 29G illustrates an example of a catheter system.

FIG. 29H illustrates another example of a catheter system.

FIG. 29I illustrates yet another example of a catheter system.

FIG. 29J illustrates still another example of a catheter system.

FIG. 29K illustrates yet still another example of a catheter system.

FIGS. 29L-29N illustrate an example method of deploying the cathetersystem of FIG. 29K.

FIG. 30A is a perspective view of an example of an electrode system.

FIG. 30B is a top plan view of a portion of the electrode system of FIG.30A.

FIG. 30C is a perspective view of another example of an electrodesystem.

FIG. 30D is a distal end view of the electrode system of FIG. 30C in acollapsed state.

FIG. 30E is a distal end view of the electrode system of FIG. 30C in anexpanded state.

FIG. 30F is a plan view of yet another example of an electrode system.

FIG. 30G is a distal end view of the electrode system of FIG. 30F.

FIGS. 31A and 31B show example electrode combinations for nineelectrodes in a 3×3 matrix.

FIGS. 31Ci-31Cxi illustrate an example method of setting a stimulationvector.

FIGS. 32A-32D show example electrode combinations for twelve electrodesin a 3×4 matrix.

FIG. 33A is a plot of contractility versus stimulation.

FIG. 33B is another plot of contractility versus stimulation.

FIG. 34 is an example process flow that can be used to implement a dutycycle method.

FIG. 35A schematically illustrates a mechanically repositionableelectrode catheter system.

FIG. 35B illustrates the catheter system of FIG. 35A after longitudinaladvancement.

FIG. 35C illustrates the catheter system of FIG. 35A after longitudinaladvancement and rotation.

FIG. 35D is a cross-sectional view taken along the line 35D-35D of FIG.35C.

FIG. 36A is a perspective view of an example of a catheter system.

FIG. 36B is a perspective view of a portion of the catheter system ofFIG. 36A in a collapsed state.

FIG. 36C is a side view of a portion of the catheter system of FIG. 36Ain an expanded state.

FIG. 36D schematically illustrates a side view of an example of anexpandable structure.

FIG. 36E schematically illustrates a side view of another example of anexpandable structure.

FIG. 36F schematically illustrates a side view of still another exampleof an expandable structure.

FIG. 36G schematically illustrates a perspective view of yet anotherexample of an expandable structure.

FIG. 36H schematically illustrates an example of an expandable structurepattern.

FIG. 36I schematically illustrates another example of an expandablestructure pattern.

FIG. 36J schematically illustrates still another example of anexpandable structure pattern.

FIG. 36K schematically illustrates yet another example of an expandablestructure pattern.

FIG. 36L schematically illustrates still yet another example of anexpandable structure pattern.

FIG. 36M schematically illustrates another example of an expandablestructure pattern.

FIG. 36N schematically illustrates an example of an expandablestructure.

FIG. 36O schematically illustrates an example of an expandable structurepattern.

FIG. 36P schematically illustrates a side view of an example of anexpandable structure.

FIG. 36Q is a proximal end view of the expandable structure of FIG. 36P.

FIG. 37A is a perspective view of an example of a catheter system.

FIG. 37B is a side view of an example of an expandable structure.

FIG. 37C is a proximal end view of the expandable structure of FIG. 37B.

FIG. 37D is a perspective view of a wire bent to form a spline pair.

FIG. 37E is a perspective view of a spline pair comprising electrodes.

FIG. 37F is an expanded perspective view of the distal end of the splinepair of FIG. 37E.

FIG. 37Fi-37Fiii illustrate an example of electrical movement ofelectrodes.

FIG. 37G is a perspective view of an example of a proximal hub of anexpandable structure.

FIG. 37H schematically illustrates a side cross-sectional view of theproximal hub of FIG. 37G.

FIG. 37I is a perspective view of a distal end of the proximal hub ofFIG. 37G.

FIG. 37J schematically illustrates a side cross-sectional view of anexample of a distal hub of an expandable structure.

FIG. 37K is a side view of an example of a proximal end of the cathetersystem of FIG. 37A.

FIG. 37L is a side cross-sectional view of the proximal end of FIG. 37K.

FIGS. 37Li-37Liii show an example method of operating a handle toradially expand an expandable member.

FIGS. 37Li and 37Liv show another example method of operating a handleto radially expand an expandable member.

FIG. 37M is a side cross-sectional view of example components of ahandle base.

FIG. 37N is a perspective view of a proximal end of an example of acatheter shaft assembly and support tube.

FIG. 37O is a side cross-sectional view of an example connection betweena distal end of a catheter shaft assembly and a proximal hub of anexpandable structure.

FIG. 37P is a perspective view of an end of an example of a hinge.

FIG. 37Q is a perspective view of an example handle of a catheter systemin an unlocked configuration.

FIG. 37R schematically illustrates a perspective cross-sectional view ofthe handle of FIG. 37Q along the line 37R-37R.

FIG. 37S is a perspective view of an example of a locking member.

FIG. 37T schematically illustrates an expanded perspectivecross-sectional view of the handle of FIG. 37Q in an unlockedconfiguration in the area of the circle 37T of FIG. 37R.

FIG. 37U is a perspective view of the handle of FIG. 37Q in a lockedconfiguration.

FIG. 37V schematically illustrates a perspective cross-sectional view ofthe handle of FIG. 37U along the line 37V-37V.

FIG. 38A is a perspective view of an example of a catheter system.

FIG. 38B is a perspective view of a portion of the catheter system ofFIG. 38A in a collapsed state.

FIG. 38C is a side view of a portion of the catheter system of FIG. 38Ain an expanded state.

FIG. 38D is a partial side cross-sectional view of an expandablestructure.

FIG. 38E is a partial side cross-sectional view of an expandablestructure.

FIG. 39A is a side view of an example of an expandable structure.

FIG. 39B is an end view of an example of another expandable structure.

FIG. 39C is an end view of an example of yet another expandablestructure.

FIG. 39D is an end view of an example of still another expandablestructure.

FIG. 40A is a perspective view of an example of a strain relief for acatheter system.

FIG. 40B is a perspective view of another example of a strain relief fora catheter system.

FIG. 41A is a perspective view of an example of a catheter system.

FIG. 41B is a perspective view of a portion of the catheter system ofFIG. 41A in a collapsed and deflated state.

FIG. 41C is a transverse cross-sectional side view of the portion ofFIG. 41B.

FIG. 41D is a side view of the portion of FIG. 41B in an inflated state.

FIG. 41E is a perspective view of the portion of FIG. 41B in an expandedstate.

FIG. 41F schematically illustrates an expandable structure expanded invasculature.

FIG. 41G schematically illustrates yet another example of an expandablestructure expanded in vasculature.

FIG. 42A is a side view of an example of an electrode structure.

FIG. 42B is a side view of another example of an electrode structure.

FIG. 43A is a side view of an example of an electrode.

FIG. 43B is a side view of another example of an electrode.

FIG. 44A is a side view of an example of an electrode.

FIG. 44B is a side view of another example of an electrode.

FIG. 45 is a diagram of neurostimulation of a nerve proximate to avessel wall.

FIG. 46A is a graph showing the monitoring of left ventriclecontractility and right ventricle contractility over time.

FIG. 46B is another graph showing the monitoring of left ventriclecontractility and right ventricle contractility over time.

FIG. 47A schematically illustrates an example electrocardiograph.

FIG. 47B is an example of a modified electrocardiograph.

FIG. 47C is an example of a monitored electrocardiograph.

FIG. 47D is an example of a modified electrocardiograph.

FIG. 47E is another example of a modified electrocardiograph.

FIG. 47F is still another example of a modified electrocardiograph.

FIG. 47G is yet another example of a modified electrocardiograph.

FIG. 47Hi schematically illustrates an example system for blankingneurostimulation from an ECG.

FIG. 47Hii schematically illustrates an example method of modifying anECG waveform.

FIG. 47Hiii schematically illustrates an example ECG waveformuncorrupted by application of neurostimulation.

FIG. 47I schematically illustrates an example system for filtering noisefrom an ECG signal.

FIG. 47J schematically illustrates an example notch filter.

FIGS. 47Ki-47Kvii schematically illustrate example effects of filteringnoise from an ECG signal.

FIG. 47L schematically illustrates an example system for matchingneurostimulation frequency to ECG monitoring frequency.

FIG. 48A illustrates insertion of a needle into vasculature.

FIG. 48B illustrates insertion of an introducer and guidewire intovasculature.

FIG. 48C illustrates a Swan-Ganz catheter and guidewire positioned inthe right pulmonary artery.

FIG. 48D illustrates an example catheter system positioned in the rightpulmonary artery in an expanded state.

FIG. 48E illustrates the catheter system of FIG. 48D in a furtherexpanded state.

FIG. 48F is a side view of a portion of a catheter system inserted intoan introducer.

FIG. 48G is a fluoroscopic image of the catheter system positioned inthe right pulmonary artery.

FIG. 48H schematically illustrates stimulation of a target nerve by theelectrodes of a catheter system positioned in the right pulmonaryartery.

FIG. 49A is a perspective view of an example expandable structure in anexpanded state.

FIG. 49Ai is a perspective view of an example expandable structure in anexpanded state.

FIG. 49Aii is a perspective view of an example expandable structure inan expanded state.

FIG. 49B is a perspective view of an example expandable structure in anexpanded state.

FIG. 49C is a perspective view of an example expandable structure in anexpanded state.

FIG. 49Ci is a perspective view of an example expandable structure in anexpanded state.

FIG. 49Cii is a perspective view of an example expandable structure inan expanded state.

FIG. 49D is a perspective view of an example expandable structure in anexpanded state.

FIG. 50A is a perspective view of an example expandable structure in anexpanded state.

FIG. 50B is a perspective view of an example expandable structure in anexpanded state.

FIG. 50C is a perspective view of an example expandable structure in anexpanded state.

FIG. 51A is a perspective view of an example expandable structure in anexpanded state.

FIG. 51B is a perspective view of an example expandable structure in acollapsed state.

FIG. 51C is a perspective view of an example expandable structure in anexpanded state.

FIG. 51D is a cross-sectional view of an example catheter for containingan expandable structure in a collapsed state.

FIGS. 51Ei-51Ev illustrate an example method of retrieving an expandablestructure.

FIG. 51Fi is a perspective view of an example expandable structure in anexpanded state.

FIG. 51Fii is a side view of the example expandable structure of FIG.51Fi.

FIG. 52Ai is a perspective view of an example expandable structure in anexpanded state.

FIG. 52Aii is a side view of the expandable structure of FIG. 52Ai in anexpanded state.

FIG. 52Aiii is an end view of the expandable structure of FIG. 52Ai inan expanded state.

FIG. 52Aiv illustrates the expandable structure of FIG. 52Ai positionedin a right pulmonary artery.

FIG. 52Bi is a perspective view of an example expandable structure in anexpanded state.

FIG. 52Bii is an end view of the expandable structure of FIG. 52Bi in anexpanded state.

FIG. 52Ci is a perspective view of an example expandable structure in anexpanded state.

FIG. 52Cii is a side view of the expandable structure of FIG. 52Ci in anexpanded state.

FIG. 52Ciii illustrates the expandable structure of FIG. 52Ci positionedin a right pulmonary artery.

FIG. 52Di is a perspective view of an example expandable structure in anexpanded state.

FIG. 52Dii is a side view of the expandable structure of FIG. 52Di in anexpanded state.

FIG. 52Diii is an end view of the expandable structure of FIG. 52Di inan expanded state.

FIG. 52E is a perspective view of an example expandable structure in anexpanded and advanced state.

FIGS. 52Fi and 52Fii illustrate an example method of using theexpandable structure of FIG. 52E.

FIG. 52Gi is a perspective view of an example expandable structure in acollapsed state.

FIG. 52Gii is a perspective view of the example expandable structure ofFIG. 52Fii in an expanded state.

FIGS. 52Giii-52Gv illustrate an example method of using the expandablestructure of FIG. 52Gi.

FIG. 52Gvi illustrates an example method of using a version of theexpandable structure 5260 comprising an electrode spline.

FIG. 53A is a perspective view of an example electrode assembly.

FIG. 53B is a scanning electron microscope image of an electrode area inthe circle 53B of FIG. 53A at 3,560× magnification.

FIGS. 53Ci-53Ciii-2 schematically illustrate an example method ofmanufacturing an electrode assembly such as the electrode assembly ofFIG. 53A.

FIGS. 53Di and 53Dii schematically illustrate another example method ofmanufacturing an example electrode assembly such as the electrodeassembly of FIG. 53A.

FIG. 53Ei schematically illustrates another example electrode assemblysuch as the electrode assembly of FIG. 53A.

FIG. 53Eii schematically illustrates another example electrode assemblysuch as the electrode assembly of FIG. 53A.

FIG. 53F is an outer perspective view of an example electrode.

FIG. 53G is an inner perspective view of the example electrode of FIG.53F.

FIG. 54A is a schematic view of a heart with an example catheter systemincluding an expandable structure deployed in the right pulmonaryartery.

FIG. 54B is a perspective view of an example pressure sensor.

FIG. 54C is a graph illustrating an example use of pressure sensors formonitoring catheter movement.

FIGS. 54Di and 54Dii illustrate an example method and system fordetecting movement of a catheter.

FIG. 54E illustrates in a single figure an example method and system fordetecting movement of a catheter.

FIG. 55 is a front view of an example stimulation system.

FIG. 56A shows a screen of an example user interface.

FIG. 56B shows another screen of the example user interface of FIG. 56A.

DETAILED DESCRIPTION

Several examples of the present disclosure provide for methods anddevices that can be used to apply electrical neuromodulation to one ormore nerves in and around the heart of a subject (e.g., patient).Several examples, for example, may be useful in electricalneuromodulation of patients with cardiovascular medical conditions, suchas patients with acute or chronic cardiac disease. As discussed herein,several examples can allow for a portion of a catheter to be positionedwithin the vasculature of the patient in at least one of the rightpulmonary artery, the left pulmonary artery, and the pulmonary trunk.Once positioned, an electrode system of the catheter can provideelectrical energy (e.g., electrical current or electrical pulses) tostimulate the autonomic nervous system surrounding (e.g., proximate to)the pulmonary artery in an effort to provide adjuvant cardiac therapy tothe patient. Sensed heart activity properties (e.g., non-electricalheart activity properties) can be used as the basis for makingadjustments to one or more properties of the one or more electricalpulses delivered through the catheter positioned in the pulmonary arteryof the heart in an effort to provide adjuvant cardiac therapy to thepatient.

Certain groups of figures showing similar items follow a numberingconvention in which the first digit or digits correspond to the drawingfigure number and the remaining digits identify an element or componentin the drawing. Similar elements or components between such groups offigures may be identified by the use of similar digits. For example, 336may reference element “36” in FIG. 3A, and a similar element “36” may bereferenced as 436 in FIG. 4A. As will be appreciated, elements shown inthe various examples herein can be added, exchanged, and/or eliminatedso as to provide any number of additional examples of the presentdisclosure. Components or features described in connection with aprevious figure may not be described in detail in connection withsubsequent figures; however, the examples illustrated in the subsequentfigures may include any of the components or combinations of componentsor features of the previous examples.

The terms “distal” and “proximal” are used herein with respect to aposition or direction relative to the treating clinician taken along thedevices of the present disclosure. “Distal” or “distally” are a positiondistant from or in a direction away from the clinician taken along thecatheter. “Proximal” and “proximally” are a position near or in adirection toward the clinician taken along the catheter.

The catheter and electrode systems of the present disclosure can be usedto treat a patient with various cardiac conditions. Such cardiacconditions include, but are not limited to, acute heart failure, amongothers. Several examples of the present disclosure provides methods thatcan be used to treat acute heart failure, also known as decompensatedheart failure, by modulating the autonomic nervous system surroundingthe pulmonary artery (e.g., the right pulmonary artery, the leftpulmonary artery, the pulmonary trunk) in an effort to provide adjuvantcardiac therapy to the patient. The neuromodulation treatment can helpby affecting heart contractility more than heart rate. The autonomicnervous system may be modulated so as to collectively affect heartcontractility more than heart rate. The autonomic nervous system can beimpacted by electrical modulation that includes stimulating and/orinhibiting nerve fibers of the autonomic nervous system.

As discussed herein, the one or more electrodes present on the cathetercan be positioned within the main pulmonary artery and/or one or both ofthe right and left pulmonary arteries. In accordance with severalexamples, the one or more electrodes are positioned in contact theluminal surface of the main pulmonary artery, and/or right or leftpulmonary artery (e.g., in physical contact with the surface of theposterior portion of the main pulmonary artery). As will be discussedherein, the one or more electrodes on the catheter and/or cathetersystem provided herein can be used to provide pulse of electrical energybetween the electrodes and/or the reference electrodes. The electrodesof the present disclosure can be used in any one of a unipolar, bi-polarand/or a multi-polar configuration. Once positioned, the catheter andthe catheter system of the present disclosure can provide thestimulation electrical energy to stimulate the nerve fibers (e.g.,autonomic nerve fibers) surrounding the main pulmonary artery and/or oneor both of the right and left pulmonary arteries in an effort to provideadjuvant cardiac therapy to the patient (e.g., electrical cardiacneuromodulation).

In some examples, systems other than intravascular catheters may be usedin accordance with the methods described herein. For example,electrodes, sensors, and the like may be implanted during open heartsurgery or without being routed through vasculature.

Several examples, as will be discussed more fully herein, may allow forthe electrical neuromodulation of the heart of the patient that includesdelivering one or more electrical pulses through a catheter positionedin a pulmonary artery of the heart of the patient, sensing from at leasta first sensor positioned at a first location within the vasculature ofthe heart one or more heart activity properties (e.g., non-electricalheart activity properties) in response to the one or more electricalpulses, and adjusting a property of the one or more electrical pulsesdelivered through the catheter positioned in the pulmonary artery of theheart in response to the one or more heart activity properties in aneffort to provide adjuvant cardiac therapy to the patient.

The catheter can include a plurality of electrodes, which are optionallyinserted into the pulmonary trunk, and positioned such that theelectrodes are, preferably, in contact with the posterior surface, thesuperior surface, and/or the inferior surface of the pulmonary artery.From such locations, electrical pulses can be delivered to or from theelectrodes to selectively modulate the autonomic nervous system of theheart. For example, electrical pulses can be delivered to or from one ormore of the electrodes to selectively modulate the autonomiccardiopulmonary nerves of the autonomic nervous system, which canmodulate heart contractility more than heart rate. Preferably, theplurality of electrodes is positioned at a site along the posterior walland/or superior wall of the pulmonary artery, for example the right orleft pulmonary artery. From such a position in the pulmonary artery, oneor more electrical pulses can be delivered through the electrodes andone or more heart activity properties (e.g., non-electrical heartactivity properties) can be sensed. Based at least in part on thesesensed heart activity properties, a property of the one or moreelectrical pulses delivered to or from the electrodes positioned in thepulmonary artery of the heart can be adjusted in an effort to positivelyinfluence heart contractility while reducing or minimizing the effect onheart rate and/or oxygen consumption. In certain examples, the effect onheart contractility is to increase heart contractility.

FIG. 1 schematically illustrates a system 100 that can be used to applyelectrical neuromodulation to tissue (e.g., including one or morenerves) in and around the heart of a subject. The system 100 comprises afirst component 102 and a second component 104. The first component 102may be positioned in a pulmonary artery (e.g., the right pulmonaryartery as shown in FIG. 1, the left pulmonary artery, and/or thepulmonary trunk). The first component 102 may be endovascularlypositioned via a minimally invasive, transdermal, percutaneousprocedure, for example routed through the vasculature from a remotelocation such as a jugular vein (e.g., an internal jugular vein, asshown in FIG. 1), an axial subclavian vein, a femoral vein, or otherblood vessels. Such an approach can be over-the-wire, using a Swan-Ganzfloat catheter, combinations thereof, etc. In some examples, the firstcomponent may be positioned invasively, for example during conventionalsurgery (e.g., open-heart surgery), placement of another device (e.g.,coronary bypass, pacemaker, defibrillator, etc.), or as a stand-aloneprocedure. As described in further detail herein, the first componentcomprises a neuromodulator (e.g., electrode, transducer, drug, ablationdevice, ultrasound, microwave, laser, cryo, combinations thereof, andthe like) and may optionally comprise a stent or framework, an anchoringsystem, and/or other components. The first component 102 may be acutelypositioned in the pulmonary artery for 24 to 72 hours. In some examples,the first component 102 neuromodulates terminal branches within thecardiac plexus, which can increase left ventricle contractility. Theincrease in left ventricle contractility may be without an increase inheart rate or may be greater than (e.g., based on a percentage change)than an increase in heart rate. In some examples, the first component102 may be adapted to ablate tissue, including nerves, in addition to orinstead of modulating tissue such as nerves.

The first component 102 is electrically coupled to the second component104 (e.g., via wires or conductive elements routed via a catheter, forexample as illustrated in FIG. 1, and/or wirelessly). The secondcomponent 104 may be positioned extracorporeally (e.g., strapped to asubject's arm as shown in FIG. 1, strapped to another part of thesubject (e.g., leg, neck, chest), placed on a bedside stand, etc.). Insome examples, the second component 104 may be temporarily implanted inthe subject (e.g., in a blood vessel, in another body cavity, in achest, etc.). The second component 104 includes electronics (e.g., pulsegenerator) configured to operate the electrode in the first component102. The second component 104 may include a power supply or may receivepower from an external source (e.g., a wall plug, a separate battery,etc.). The second component 104 may include electronics configured toreceive sensor data.

The system 100 may comprise a sensor. The sensor may be positioned inone or more of a pulmonary artery (e.g., right pulmonary artery, leftpulmonary artery, and/or pulmonary trunk), an atrium (e.g., right and/orleft), a ventricle (e.g., right and/or left), a vena cava (e.g.,superior vena cava and/or inferior vena cava), and/or othercardiovascular locations. The sensor may be part of the first component102, part of a catheter, and/or separate from the first component 102(e.g., electrocardiogram chest monitor, pulse oximeter, etc.). Thesensor may be in communication with the second component 104 (e.g.,wired and/or wireless). The second component 104 may initiate, adjust,calibrate, cease, etc. neuromodulation based on information from thesensor.

The system 100 may comprise an “all-in-one” system in which the firstcomponent 102 is integral or monolithic with the targeting catheter. Forexample, the first component 102 may be part of a catheter that isinserted into an internal jugular vein, an axial subclavian vein, afemoral vein, etc. and navigated to a target location such as thepulmonary artery. The first component 102 may then be deployed from thecatheter. Such a system can reduce the number and/or complexity ofprocedural steps and catheter exchanges used to position the firstcomponent 102. For example, a guidewire may be at least twice as long asa target catheter, which can be difficult to control in a sterile field.Such a system may make repositioning of the first component 102 easierafter an initial deployment because positioning systems are already inplace.

The system 100 may comprise a telescoping and/or over-the-wire system inwhich the first component 102 is different than the targeting catheter.For example, a targeting catheter (e.g., a Swan-Ganz catheter) may beinserted into an internal jugular vein, an axial subclavian vein, afemoral vein, etc. and navigated to a target location such as thepulmonary artery (e.g., by floating). A guidewire may be inserted into aproximal hub through the target catheter to the target location (e.g.,having a stiffest portion exiting the target catheter distal end) andthe first component 102 as part of a separate catheter than the targetcatheter may be tracked to the target location over the guidewire orusing telescoping systems such as other guidewires, guide catheters,etc. The first component 102 may then be deployed from the separatecatheter. Such systems are known by interventional cardiologists suchthat multiple exchanges may be of little issue. Such a system may allowcustomization of certain specific functions. Such a system may reduceoverall catheter diameters, which can increase trackability, and/orallow additional features to be added, for example because not allfunctions are integrated into one catheter. Such a system may allow useof multiple catheters (e.g., removing a first separate catheter andpositioning a second separate catheter without having to reposition theentire system). For example, catheters with different types of sensorsmay be positioned and removed as desired. The system 100 may besteerable (e.g., comprising a steerable catheter) without a Swan-Ganztip. Some systems 100 may be compatible with one or more of thedescribed types of systems (e.g., a steerable catheter with anoptionally inflatable balloon for Swan-Ganz float, a steerable catheterthat can be telescoped over a guidewire and/or through a catheter,etc.).

FIG. 2A schematically illustrates a heart 200 and surrounding areas. Themain pulmonary artery or pulmonary trunk 202 begins at the outlet of theright ventricle 204. In an adult, the pulmonary trunk 202 is a tubularstructure having a diameter of about 3 centimeter (cm) (approx. 1.2inches (in)) and a length of about 5 (approx. 2.0 in). The mainpulmonary artery 202 branches into the right pulmonary artery 206 andthe left pulmonary artery 208, which deliver deoxygenated blood to thecorresponding lung. As illustrated in FIG. 2A, the main pulmonary artery202 has a posterior surface 210 that arches over the left atrium 212 andis adjacent to the pulmonary vein 213. As discussed herein, aneurostimulator can be positioned at least partially in a pulmonaryartery 202, 206, 208, for example with the neurostimulator in contactwith the posterior surface 210. In some examples, a preferred locationfor positioning the neurostimulator is the right pulmonary artery 204.PCT Patent App. No. PCT/US2015/047780 and U.S. Provisional Patent App.No. 62/047,313 are incorporated herein by reference in their entirety,and more specifically the descriptions of positioning in the rightpulmonary artery disclosed therein are incorporated herein by reference.In some examples, a preferred location for positioning theneurostimulator is in contact with the posterior surface 210 of thepulmonary artery 202, 206, 208. From such a location, stimulationelectrical energy delivered from an electrode, for example, may bebetter able to treat and/or provide therapy (including adjuvant therapy)to a subject experiencing a variety of cardiovascular medicalconditions, such as acute heart failure. Other locations for theneurostimulator in the pulmonary artery 202, 206, 208 are also possible.

The first component 102 (FIG. 1) can be positioned in the pulmonaryartery 202, 206, 208 of the subject, where the neurostimulator of thefirst component 102 is in contact with the luminal surface of thepulmonary artery 202, 206, 208 (e.g., in physical contact with orproximate to the surface of the posterior portion 210 of the pulmonaryartery 202, 206, 208). The neurostimulator of the first component 102can be used to deliver the stimulation to the autonomic cardiopulmonaryfibers surrounding the pulmonary artery 202, 206, 208. The stimulationelectrical energy can elicit responses from the autonomic nervous systemthat may help to modulate a subject's cardiac contractility. Thestimulation may affect contractility more than the heart rate, which canimprove hemodynamic control while possibly reducing unwanted systemiceffects.

In some examples, neuromodulation of targeted nerves or tissue asdescribed herein can be used for the treatment of arrhythmia, atrialfibrillation or flutter, diabetes, eating disorders, endocrine diseases,genetic metabolic syndromes, hyperglycemia (including glucosetolerance), hyperlipidemia, hypertension, inflammatory diseases, insulinresistance, metabolic diseases, obesity, ventricular tachycardia,conditions affecting the heart, and/or combinations thereof.

FIGS. 2B-2D are schematic illustrations of a heart 200 and surroundingareas from various perspectives. Portions of the heart 200 (e.g., theaorta, the superior vena cava, among other structures), including aportion of the pulmonary trunk 202, have been removed to allow for thedetails discussed herein to be shown. FIG. 2B provides a perspectiveview of the heart 200 as seen from the front of the subject or patient(viewed in an anterior to posterior direction), while FIG. 2C provides aperspective view of the heart 200 as seen from the right side of thesubject. As illustrated, the heart 100 includes the pulmonary trunk 102that begins at the base of the right ventricle 104. In an adult, thepulmonary trunk 102 is a tubular structure approximately 3 centimeters(cm) in diameter and 5 cm in length. The pulmonary trunk 202 branchesinto the right pulmonary artery 206 and the left pulmonary artery 208 ata branch point or bifurcation 207. The left pulmonary artery 106 and theright pulmonary artery 108 serve to deliver de-oxygenated blood to eachcorresponding lung.

The branch point 207 includes a ridge 209 that extends from theposterior of the pulmonary trunk 202. As illustrated, the branch point207, along with the ridge 209, provides a “Y” or “T” shaped structurethat helps to define at least a portion of the left pulmonary artery 208and the right pulmonary artery 206. For example, from the ridge 209, thebranch point 207 of the pulmonary trunk 202 slopes in oppositedirections. In a first direction, the pulmonary trunk 202 transitionsinto the left pulmonary artery 208, and in the second direction,opposite the first direction, the pulmonary trunk 202 transitions intothe right pulmonary artery 206. The branch point 207 may not necessarilybe aligned along a longitudinal center line 214 of the pulmonary trunk202.

As illustrated in FIG. 2B, portions of the pulmonary artery 202 can bedefined with a right lateral plane 216 that passes along a right luminalsurface 218 of the pulmonary trunk 202, a left lateral plane 220parallel with the right lateral plane 216, where the left lateral plane220 passes along a left luminal surface 222 of the pulmonary trunk 202.The right lateral plane 216 and the left lateral plane 220 extend inboth a posterior direction 224 and anterior direction 226. Asillustrated, the ridge 209 of the branch point 207 is located betweenthe right lateral plane 216 and the left lateral plane 220. The branchpoint 207 is positioned between the right lateral plane 216 and the leftlateral plane 220, where the branch point 207 can help to at leastpartially define the beginning of the left pulmonary artery 208 and theright pulmonary artery 206 of the heart 200. The distance between theright lateral plane 216 and the left lateral plane 220 is approximatelythe diameter of the pulmonary trunk 202 (e.g., about 3 cm).

As discussed herein, the present disclosure includes methods forneuromodulation of the heart 200 of a subject or patient. For example,as discussed herein, a catheter positioned in the pulmonary artery 202can be used to deliver one or more electrical pulses to the heart 200. Afirst sensor, for example as discussed herein, positioned at a firstlocation within the vasculature of the heart 200, senses a heartactivity property in response to the neurostimulation. Properties of theneurostimulator can be adjusted in response to the sensed heart activityproperty in an effort to provide adjuvant cardiac therapy to thepatient.

FIG. 2D provides an additional illustration the posterior surface 221,the superior surface 223, and the inferior surface 225 of the rightpulmonary artery 206. As illustrated, the view of the heart 200 in FIG.2D is from the right side of the heart 200. As illustrated, theposterior surface 221, the superior surface 223, and the inferiorsurface 225 account for approximately three quarters of the luminalperimeter of the right pulmonary artery 206, where the anterior surface227 accounts for the remainder. FIG. 2D also illustrates the aorta 230,pulmonary veins 213, the superior vena cava (SVC) 232, and the inferiorvena cava (IVC) 234.

FIGS. 2E and 2F are schematic illustrations of a heart 200 andsurrounding nerves. The cardiovascular system is richly innervated withautonomic fibers. Sympathetic fibers originate from stellate andthoracic sympathetic ganglia, and are responsible for increases in thechronotropic (heart rate), lusotropic (relaxation), and inotropic(contractility) state of the heart. Human cadaver anatomical studiesshow that the fibers responsible for the lusotropic and inotropic stateof the ventricles pass along the posterior surface of the rightpulmonary artery 206 and the pulmonary trunk 202. FIG. 2E illustratesapproximate positions of the right dorsal medial common peroneal nerve(CPN) 240, the right dorsal lateral CPN 242, the right stellate CPN 244,the right vagal nerve or vagus 246, the right cranial vagal CPN 248, theright caudal vagal CPN 250, the right coronary cardiac nerve 252, theleft coronary cardiac nerve 254, the left lateral cardiac nerve 256, theleft recurrent laryngeal nerve 258, the left vagal nerve or vagus 260,the left stellate CPN 262, the left dorsal lateral CPN 264, and the leftdorsal medial CPN 266. These and/or other nerves surrounding (e.g.,proximate to) the heart 200 can be targeted for neurostimulation by thesystems and methods described herein. In some examples, at least one ofthe right dorsal medial common peroneal nerve 240, the right stellateCPN 244, and the left lateral cardiac nerve 256 is targeted and/oraffected for neuromodulation, although other nerves, shown in FIG. 2E orotherwise, may also be targeted and/or affected.

FIGS. 2E and 2F also schematically illustrate the trachea 241. As bestseen in FIG. 2F, the trachea 241 bifurcates into the right pulmonarybronchus 243 and the left pulmonary bronchus 241. The bifurcation of thetrachea 241 can be considered along a plane 245. The plane 245 is alongthe right pulmonary artery 206. The bifurcation of the pulmonary arterycan be considered along a plane 247, which is spaced from the plane 245by a gap 249. The gap 249 spans the right pulmonary artery 206. A largenumber of cardiac nerves cross the right pulmonary artery 206 along thegap 249 as illustrated by the circled area 251, and these nerves may beadvantageously targeted by some of the systems and methods describedherein. In certain such examples, the bifurcation of the trachea 241and/or the bifurcation of the pulmonary artery 202 may provide alandmark for system and/or component positioning. Stimulation electrodesmay be spaced from the trachea 241, for example to reduce cough or otherpossible respiratory side effects. In some examples, stimulationelectrodes are spaced from the trachea 241 or the plane 245 by betweenabout 2 mm and about 8 mm (e.g., about 2 mm, about 3 mm, about 4 mm,about 5 mm, about 6 mm, about 7 mm, about 8 mm, ranges between suchvalues, etc.). In some examples, stimulation electrodes are spaced fromthe trachea 241 or the plane 245 by a percentage of a length of theright pulmonary artery 206 between about 10% and about 100% (e.g., about10%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%,about 55%, about 75%, about 100%, ranges between such values, etc.).

FIGS. 2G and 2H are schematic illustrations of vasculature and anelectrode matrix 201. A majority of the electrode matrix 201 ispositioned in the right pulmonary artery 206, although some of theelectrode matrix 201 may be considered positioned in the pulmonary trunk202. The electrode array is shown as a 4×5 matrix of electrodes 203. Asdescribed in further detail herein, the electrodes 203 may be positionedon splines, positioned on a membrane or mesh coupled to splines, etc.For example, four splines may each contain five electrodes 203. In someexamples, the electrodes 203 comprise bipolar electrodes withcontrollable polarity, allowing configurability of the electrode matrix201. In some examples, edge-to-edge spacing of the electrodes 203 isbetween about 3 mm and about 7 mm (e.g., about 3 mm, about 4 mm, about 5mm, about 6 mm, about 7 mm, ranges between such values, etc.). In someexamples, the electrodes 203 have a surface area between about 0.5 mm²and about 5 mm² (e.g., about 0.5 mm², about 1 mm², about 1.5 mm², about2 mm², about 2.5 mm², about 3 mm², about 3.5 mm², about 4 mm², about 4.5mm², about 5 mm², ranges between such values, etc.). The electrodes 203are generally aligned longitudinally and circumferentially, but offsetelectrodes 203 are also possible. The coverage of the right pulmonaryartery 206 provided by the electrode array 201 is longitudinally betweenabout 25 mm and about 35 mm (e.g., about 25 mm, about 28 mm, about 31mm, about 35 mm, ranges between such values, etc.) and iscircumferentially between about 80° and about 120° (e.g., about 80°,about 90°, about 100°, about 110°, about 120°, ranges between suchvalues, etc.). The electrode array 201 may cover, for example, betweenabout 25% and about 50% (e.g., about 25%, about 30%, about 35%, about40%, about 45%, about 50%, ranges between such values, etc.) of thecircumference of the vessel. In some examples, the electrode array 201comprises a 3×3 matrix, a 3×4 matrix, a 3×5 matrix, a 4×4 matrix, a 4×5matrix, or a 5×5 matrix. Larger matrices may be more likely to capturethe target nerve by at least one combination of electrodes 203, andsmaller matrices may be easier to deliver to the target site.

FIG. 2I is a schematic illustration of heart vasculature and surroundingnerves. Similar to FIGS. 2G and 2H, FIG. 2I shows a pulmonary trunk 202,a right pulmonary artery 206, and a left pulmonary artery 208. FIG. 2Ialso shows traces of the approximate crossing locations ofinterventricular sulcus nerves 215, 217 along the right pulmonary artery206 and the pulmonary trunk 202. Stimulation of one or both of thenerves 215, 217 may increase contractility, for example more than heartrate or without affecting heart rate. The electrode matrix 201,including electrodes 203 a, 203 b, 203 c, 203 d, 203 e, 203 f, etc., isshown in phantom in the approximate position of FIGS. 2G and 2H.

In some examples, particular electrodes can be selected to target orcapture one or more nerves. The electrodes 203 a, 203 b can be used totarget the nerve 215, for example, in a generally transverse manner. Theelectrodes 203 a, 203 c can be used to target the nerve 215, forexample, in a generally parallel manner. The electrodes 203 c, 203 d canbe used to target the nerve 215 as well as the nerve 217, for example,in a generally transverse manner. The electrodes 203 e, 203 f can beused to target the nerve 217, for example, in a generally mixedtransverse-parallel manner. In some examples, the two electrodes can beused in a bipolar manner, with one of the two electrodes being positiveand the other of the two electrodes being negative. In some examples,more than two electrodes can be used, with two or more electrodes beingpositive and two or more electrodes being negative.

As described in further detail herein, upon placement of the electrodearray, electrode combinations can be stimulated to test their effect.Some combinations may produce a better result but be more likely toresult in a side effect, some combinations may produce a better resultbut be less repeatable, some combinations may affect one nerve but notmultiple nerves, etc. In some examples, a plurality of electrodecombinations or independent outputs can be used in parallel or inseries. For example, the electrodes 203 a, 203 b can be used to targetthe nerve 215 for a first duration and the electrodes 203 e, 203 f canbe used to target the nerve 217 for a second duration. The secondduration may at least partially overlap the first duration, fullyoverlap the first duration (e.g., starting at the same time, ending atthe same time, starting after the first duration starts, ending beforethe first duration ends, and combinations thereof) or may be temporallyspaced from the first duration by a third duration. The third durationmay be zero (e.g., the second duration starting as the first durationends).

In a study of multiple cadavers, the mean diameter 206 d of the rightpulmonary artery 206 proximate to the branch point 207 was about 26.5 mmwith a standard deviation of about 4.6 mm. Assuming a circular vessel,the mean circumference of the right pulmonary artery 206 proximate tothe branch point 207 is about 83 mm. If the goal is 30% coverage of thecircumference, then an electrode matrix should have a circumferentiallength of about 25 mm (83 mm×30%). Other electrode matrix dimensions canbe estimated or calculated based on other dimensions (e.g., vesseldiameter at other points, measured vessel diameter, diameters of othervessels, vessel lengths, etc.), target coverage percentage, nervelocation variability, placement accuracy, stimulation parameters, etc.

FIG. 2J is a schematic illustration of vasculature and surroundingnerves. The superior vena cava 232, as discussed above, supplies bloodto the right atrium of the heart. The vessels supplying blood to thesuperior vena cava 232 include the right innominate vein or rightbrachiocephalic vein 253 and the left innominate vein or leftbrachiocephalic vein 255. The vessels supplying blood to the rightbrachiocephalic vein 253 include the right subclavian vein 257 and theright internal jugular vein 259. The vessels supplying blood to the leftbrachiocephalic vein 255 include the left subclavian vein 261 and theleft internal jugular vein 263. The inferior thyroid vein 265 alsosupplies blood to the superior vena cava 232. Although other nerves arepresent surrounding the vasculature illustrated in FIG. 2F, the rightvagus nerve 267 is illustrated as an example. The left vagus nerve runsclose to the left internal jugular vein 263 and the common carotidartery, and then crosses the left brachiocephalic vein 255. Thoracicsympathetic cardiac branches also cross the left brachiocephalic vein255 closer to the crown of the aorta and more medial, generally betweenthe junction of the left subclavian vein and the left internal jugularvein 263 and about half of the length of the left brachiocephalic vein253. Vasculature that may not typically be characterized ascardiovasculature may also be used in accordance with certain methodsand systems described herein.

FIG. 2K is another schematic illustration of a heart 200 and surroundingnerves. As described in detail herein, nerves affecting contractility(e.g., left ventricle contractility) may be targeted for neuromodulationby positioning a catheter in the pulmonary artery (e.g., right pulmonaryartery, pulmonary trunk, left pulmonary artery). In some examples, anerve such as the right stellate CPN 244 may also or alternatively betargeted by positioning a device at a location 272 in the leftsubclavian artery 274 and/or the location 276 in the descending aorta278. Positioning in the left common carotid artery 280 is also possible.In FIG. 2K, an example stimulation device 282 is shown at the locations272, 276. Other stimulation devices are also possible. In examplescomprising multiple stimulation devices, the stimulation devices may bethe same, different, or similar (as a non-limiting example, having asame structure but different dimensions).

FIG. 2L illustrates an example stimulation device 282. The stimulationdevice 282 may be used, for example, to target stimulation of a rightstellate CPN 244 or another nerve. The device 282 comprises a skeletalstructure 284, for example a stent, hoops, etc. The skeletal structure284 may comprise a shape memory material (e.g., nitinol) that isself-expanding. The device 282 further comprise a mesh or membrane 286attached to the skeletal structure 284. The mesh 286 may comprise, forexample, Dacron®. One side of the device 282 comprises an electrodearray 288. The electrode array 288 may have an area between about 0.5cm² and about 3 cm² (e.g., about 0.5 cm², about 1 cm², about 1.5 cm²,about 2 cm², about 2.5 cm², about 3 cm², ranges between such values,etc.). The electrode array 288 may be powered by implantable electronics290. The electronics 290 may include, for example, non-volatile memory(e.g., storing electrode combinations and parameters), ASIC stimulationengine and logic, RF engine, battery power, and a sensor (e.g., pressuresensor, contractility sensor, combinations thereof, etc.). The device282 may be positioned by a catheter routed through vasculature (e.g.,from a femoral or radial artery). The device 282 may be positionableuntil the target nerve is stimulated. In some examples, the electrodearray 288 may be electronically repositionable (e.g., as described withrespect to FIGS. 32A-32D). In some examples, an external device (e.g.,worn by the subject) can power and/or control the device 282. Inexamples in which the electronics 290 can power and/or control thedevice 282, the device 282 may be fully implantable. In certain suchexamples, the device 282 may be combined with a pacemaker,defibrillator, or other implantable stimulation device.

FIG. 3A is a side perspective and partial cross-sectional view of anexample of a catheter 300. FIG. 3B is a distal end view of the catheter300 of FIG. 3A as viewed along line 3B-3B in FIG. 3A. The catheter 300includes an elongate body 302 having a first for proximal end 304 and asecond or distal end 306. The second end 306 is distal to the first end304. The elongate body 302 includes a longitudinal axis 308 that extendsthrough the first end 304 and the second end 306 of the elongate body302. A first plane 310 extends through the longitudinal axis 308 overthe length of the elongate body 302. As used herein, a plane is animaginary flat surface on which a straight line joining any two pointson it would wholly lie, and is used herein to help orientate therelative position of structures on the catheter 300. The first plane 310is used herein, among other reasons, to help explain the relativeposition of electrodes. The catheter 300 further includes at least twoelongate stimulation members 314 (as illustrated in FIGS. 3A and 3B, 314a and 314 b). The stimulation members 314 extend from the elongate body302. Each of the at least two elongate stimulation members 314 a, 314 bcurves into a first volume 316 defined at least in part by the firstplane 310. For example, the at least two elongate stimulation members314 extend from approximately the second end 306 of the elongate body302 into the first volume 316.

Each of the at least two elongate stimulation members 314 comprises atleast one electrode 318. The at least one electrode 318 on each of theelongate stimulation members 314 form an electrode array in the firstvolume 316 that is at least partially defined by the first plane 310.The at least one electrode 318 on each of the stimulation members 314are electrically isolated from one another. In some examples, thestimulation members 314 comprise an electrically insulating material.

Each of the at least one electrodes 318 is coupled to a correspondingconductive element 320. The conductive elements 320 are electricallyisolated from each other and extend through and/or along the stimulationmembers 314 from each respective electrode 318 through the first end 304of the elongate body 302. The conductive elements 320 terminate at aconnector port, where each of the conductive elements 320 can bereleasably coupled to a stimulation system, for example as discussedherein. In some examples, the conductive elements 320 are permanentlycoupled to the stimulation system (e.g., not releasably coupled). Thestimulation system can be used to provide stimulation electrical energythat is conducted through the conductive elements 320 and deliveredacross combinations of the electrodes 318 in the electrode array.

Each of the at least two elongate stimulation members 314 includes astimulation member elongate body 322 having a distal end 324. The distalend 324 of the stimulation member elongate body 322 for each of theelongate stimulation members 314 extends from the elongate body 302.Each of the elongate body 302 and the stimulation member elongate body322 include a surface defining a lumen 328 through which a wire 326 mayextend. The wire 326 is joined to its respective stimulation memberelongate body 322 at or near the distal end 324 of the stimulationmember elongate body 322, where the wire 326 then freely extends throughthe lumen 328 in the elongate stimulation member 314 past the first end304 of the elongate body 302. The lumen 328 is dimensioned to allow thewire 326 to be moved longitudinally within the lumen 328. The portion ofthe wire 326 extending from the first end 304 can be used to applypressure against the stimulation member elongate body 322 at or near thedistal end 324 of the stimulation member elongate body 322, where thewire 326 under such pressure can deflect or bend, which can impart acurve into each of the at least two elongate stimulation members 314into the first volume 316 defined at least in part by the first plane310. The at least two elongate stimulation members 314 extend radiallyaway from the elongate body 302 over a range of distances depending uponhow much pressure is applied to the wires 326. The curves of the atleast two elongate stimulation members 314 can have a radius ofcurvature that changes along the length of the stimulation memberelongate body 322 (e.g., as illustrated in FIG. 3A).

In some examples, the at least two elongate stimulation members 314 onlycurve in the first volume 316 defined at least in part by the firstplane 310. A second volume 330 opposite the first volume and defined atleast in part by the first plane 310 may contain no electrodes. In someexamples, the at least two elongate stimulation members 314 include afirst elongate stimulation member 314 a and a second elongatestimulation member 314 b. A second plane 312 perpendicularly intersectsthe first plane 310 along the longitudinal axis 308 of the elongate body302. The first plane 310 and the second plane 312 divide the firstvolume 316 into a first quadrant volume 332 and a second quadrant volume334. In some example examples—(e.g., as illustrated in FIGS. 3A and 3B),the first elongate stimulation member 314 a curves into the firstquadrant volume 332 and the second elongate stimulation member 314 bcurves into the second quadrant volume 334.

The catheter 300 may include an anchor member 336 that extends from theelongate body 302 into the second volume 330. The anchor member 336 maynot include or be devoid of an electrode. The anchor member 336 is notocclusive within vasculature and/or does not encourage thrombosis orcoagulation of blood within vasculature. The anchor member 336 and theelongate body 302 include surfaces defining a lumen 338 through whichwire 340 can pass. The wire 340 is joined to the anchor member 336 at ornear a distal end 342 of the member 336, where the wire 340 freelyextends through the lumen 338 of the anchor member 336 past the firstend 304 of the elongate body 302. The lumen 338 is dimensioned to allowthe wire 340 to be moved longitudinally within the lumen 338. Theportion of the wire 340 extending from the first end 304 can be used toapply pressure against the anchor member 336 at or near its distal end342, where the wire 340 under such pressure can deflect or bend, whichcan impart a curve into the anchor member 336. The anchor member 336 canextend radially away from the elongate body 302 over a range ofdistances depending upon how much pressure is applied to the wire 340.The anchor member 336 can be used to bring the electrodes 318 intocontact with a vascular luminal surface (e.g., a posterior surface ofthe main pulmonary artery and/or one or both of the pulmonary arteries),for example as described herein, by application of a variety ofpressures. Optionally, the anchor member 336 can be configured toinclude one or more electrodes.

Each of the wires 326 and the wire 340, upon being used to impart thecurves in their respective members, can then be releasably locked inplace by inhibiting or preventing longitudinal movement of the wire 326,340 relative the elongate body 302. For example, a clamp or other devicecan be used to create contact between the wire 326, 340 and the surfaceof the lumen 328, 338 sufficient to inhibit or prevent the wire 326, 340from moving relative the surface of the lumen 328, 338. This clampingaction can also function as a hemostasis valve to reduce or minimizeblood loss.

FIGS. 3A and 3B also illustrate a pulmonary artery catheter 344(partially shown to show detail of catheter 300) that can be used withthe catheter 300 in a catheter system. The pulmonary artery catheter 344includes an elongate catheter body 346 having a first or proximal end348, a second or distal end 350, a peripheral surface 352, and aninterior surface 354 opposite the peripheral surface 352. The interiorsurface 354 at least partially defines a lumen 356 that extends betweenthe first end 348 and the second end 350 of the elongate catheter body346. The lumen 356 is of a sufficient size and shape to house at least aportion of the catheter 300 inside the lumen 356 during delivery of thecatheter 300. For example, the anchor member 336 and the at least twoelongate stimulation members 314, along with a least a portion of theelongate body 302, can be positioned at least partially n the lumen 356.The anchor member 336, the at least two elongate stimulation members314, and at least a portion of the elongate body 302 can be deployedfrom the distal end 350 of the pulmonary artery catheter 344 during thedelivery and implantation of the catheter 300.

The pulmonary artery catheter 344 can further include an inflatableballoon 358 on the peripheral surface 352 of the elongate catheter body346. The inflatable balloon 358 includes a balloon wall 360 having aninterior surface 362 that, along with a portion of the peripheralsurface 352 of the elongate catheter body 346, at least partiallydefines a fluid-tight volume 364. The pulmonary artery catheter 344further includes an inflation lumen 366 that extends through theelongate catheter body 346. The inflation lumen 366 includes a firstopening 368 into the fluid-tight volume 364 of the inflatable balloon358 and a second opening 370 proximal to the first opening 368 to allowfor a fluid to move in and out of the fluid tight volume 364 to inflateand deflate the balloon 358, respectively. A syringe or other suchdevices containing the fluid (e.g., saline, contrast, gas (e.g.,oxygen)) can be used to inflate and deflate the balloon 358. FIG. 3Ashows the balloon 358 in an inflated state, while FIG. 3B shows theballoon 358 in a deflated state.

The catheter system can be used to position the catheter 300 in the mainpulmonary artery and/or one or both of the pulmonary arteries of thepatient, for example as described herein. The pulmonary artery catheter344, with the catheter 300 positioned within the lumen 356, can beintroduced into the vasculature through a percutaneous incision andguided to the right ventricle. For example, the catheter 300 can beinserted into the vasculature via a peripheral vein of the arm (e.g., aswith a peripherally inserted central catheter). Changes in a subject'selectrocardiography and/or pressure signals from the vasculature can beused to guide and locate the catheter 300 within the subject's heart.Once in the proper location, the balloon 358 can be inflated to allowthe pulmonary artery catheter 344 and the catheter 300 to be carried bythe flow of blood from the right ventricle to the main pulmonary arteryand/or one of the pulmonary arteries. Optionally, various imagingmodalities can be used in positioning the catheter 300 and/or cathetersystem in the main pulmonary artery and/or one of the pulmonaryarteries. Such imaging modalities include, but are not limited to,fluoroscopy, ultrasound, electromagnetic, and electropotentialmodalities.

The catheter system can be advance along the main pulmonary artery untilthe distal end 350 of the pulmonary artery catheter 344 contacts the topof the main pulmonary artery (e.g., a location distal to the pulmonaryvalve and adjacent to both of the pulmonary arteries). The advancementcan be with the balloon 358 in the inflated or deflated state. Once thedistal end 350 of the pulmonary artery catheter 344 reaches the top ofthe main pulmonary artery, the elongate catheter body 346 can be movedrelative the catheter 300 so as to deploy the catheter 300 from thelumen 356 of the pulmonary artery catheter 344.

The peripheral surface of the catheter body 302 may include markings,for example starting and extending from the first end 304 towards thesecond end 306 of the catheter 300. The distance between the markingscan be of units (e.g., millimeters, inches, etc.), which can allow thelength between the distal end 350 of the pulmonary artery catheter 344and the top of the main pulmonary artery to be determined. A marking canalso or alternatively be provided on the peripheral surface of thecatheter body 302 that indicates when the distal end 350 of thepulmonary artery catheter 344 is clear of the anchor member 336 and theelongate stimulation members 314. In some examples, a positioning gaugecan be used to locate the catheter 300 within the main pulmonary artery,for example as discussed in further detail herein.

The ability to measure distance from the top of the main pulmonaryartery may be helpful in placing the electrodes 318 in a desiredlocation in the main pulmonary artery. In addition or alternative tomeasuring the distance from which the second end 306 of the elongatebody 302 is placed from the top of the main pulmonary artery, theelongate body 302 can also be used to identify or map a position (e.g.,a desired or optimal position) for the electrodes 314 within thevasculature. For example, the second end 306 of the elongate body 302can be positioned at a desired distance from the top of the mainpulmonary artery using the markings on the peripheral surface of thecatheter body 302. The wires 326 and 340 can then be used to impart thecurves into the elongate stimulation members 314 and the anchor member336. Using the wires 326 and the wire 340, the elongate stimulationmembers 314 and the anchor member 336 can be imparted with curves ofsufficient size to contact a surface of the main pulmonary artery, suchas the anterior surface of the main pulmonary artery, which can bringthe electrodes 318 into contact with the main pulmonary artery or one ofthe pulmonary arteries (the left pulmonary artery or the right pulmonaryartery). The anchor member 336, as will be appreciated, biases and helpsto anchor the electrodes 318 along the vessel surface (e.g., along theposterior surface of the main pulmonary artery or one of the pulmonaryarteries (the left pulmonary artery or the right pulmonary artery)).

Due to its adjustable nature (e.g., depending at least partially on howmuch pressure or longitudinal force is applied to the wire 340), theanchor member 336 can be used to bring the electrodes 318 into contactwith the luminal surface of the main pulmonary artery or one of thepulmonary arteries with a variety of pressures. For example, the anchormember 336 can bring the electrodes 318 into contact with the luminalsurface of the main pulmonary artery or one of the pulmonary arterieswith a first pressure. Using the stimulation system, for example asdiscussed herein, stimulation electrical energy can be delivered acrosscombinations of two or more of the at least one electrode 318 in theelectrode array. It is possible for the subject's cardiac response tothe stimulation electrical energy to be monitored and recorded forcomparison to other subsequent tests.

For any of the catheters and/or catheter systems discussed herein, anycombination of electrodes, including reference electrodes (e.g., asdiscussed herein), positioned n or on the subject's body, can be used inproviding stimulation to and sensing cardiac signals from the subject.

The pressure may be reduced and the elongate body 302 can be rotated ineither a clockwise or counter-clockwise direction to reposition theelectrodes 318 in contact with the luminal surface of the main pulmonaryartery or one of the pulmonary arteries. The stimulation system can beused to deliver stimulation electrical energy across combinations of twoor more of the at least one electrode 318 in the electrode array. Thesubject's cardiac response to this test can then be monitored andrecorded for comparison to previous and/or subsequent tests. In thisway, a preferred location for the position of the electrodes 318 alongthe luminal surface of the main pulmonary artery or one of the pulmonaryarteries can be identified. Once the preferred location for the positionof the electrodes 318 has been identified, the wire 340 can be used toincrease the pressure applied by the anchor member 336, which can helpto further anchor the catheter 300 in the patient.

FIG. 4A is a side perspective and partial cross-sectional view ofanother example of a catheter 400. FIG. 4B is a distal end view of thecatheter 400 of FIG. 4A as viewed along line 4B-4B in FIG. 4A. Thecatheter 400 includes at least the structures as discussed herein withrespect to the catheter 300, so a detailed discussion of shared orsimilar elements is not repeated but the element numbers are incrementedin the hundreds place in FIGS. 4A and 4B with the understanding that thediscussion of these elements is implicit.

Each of the at least two elongate stimulation members 414 comprises aplurality of electrodes 418 (e.g., three electrodes 418 as illustratedin FIGS. 4A and 4B, although other numbers (e.g., one, two, four, five,or more) are also possible). The electrodes 418 on the elongatestimulation members 414 form an electrode array. The electrodes 418 oneach of the stimulation members 414 are electrically isolated from oneanother.

The catheter 400 further includes a structure 472 extending between atleast two of the least two elongate stimulation members 414. Thestructure 472 is flexible such that it can transition between a deliveryor low-profile state (radially folded state) that allows the structure472 to be delivered into the main pulmonary artery and/or one of thepulmonary arteries, and a deployed or expanded state (radially expanded)as illustrated in FIG. 4A. The wires 426 and the least two elongatestimulation members 414 can be used to bring the structure 472 into itsdeployed or expanded state, for example as described herein. An exampleof the structure 472 is a mesh structure.

The structure 472 comprises a plurality of flexible strands that areconnected to form a pattern of openings between the strands. One or moreelectrodes 474 can be present at one or more of the connections of thestrands. The electrodes 474 can themselves form an electrode array, ortogether with the electrodes 418 may form an electrode array. Inexamples comprising a plurality of electrodes 474, the electrodes 474can be aligned (e.g., as illustrated in FIG. 4A), in a two-dimensionalpattern, in a three-dimensional pattern (e.g., accounting for thecurvature of the stimulation member elongate body 422), or scatteredwithout a specific order. The strands can comprise the same material asthe elongate body 402 and/or the elongate stimulation members 414 ormaterial that is different than the elongate body 402 and/or theelongate stimulation members 414. The strands may comprise insulativematerial. Examples of insulative material for one or more portions ofthe catheters and structures provided herein can include, but are notlimited to, medical grade polyurethanes, such as polyester-basedpolyurethanes, polyether-based polyurethanes, and polycarbonate-basedpolyurethanes; polyamides, polyamide block copolymers, polyolefins suchas polyethylene (e.g., high-density polyethylene, low-densitypolyethylene), and polyimides, among others.

The structure 472 can have a predefined shape that helps to locate andposition at least one of the elongate stimulation members 414 and theelectrodes 418 thereon. For example, the structure 472 can be used toadjust and/or maintain the distance between electrodes 418 on theadjacent stimulation members 414.

The structure 472 can include one or more additional electrode 474. Theadditional electrode 474 can either be positioned on the structure 472or formed as an integral part of the structure 472. Each of theadditional electrodes 474 may be electrically isolated from each of theother electrodes 474 and/or the electrodes 418. The additionalelectrodes 474 each include a conductive element 476. Each of theconductive elements 476 is electrically isolated from each other and canextend through the strands of the structure 472 from each respectiveadditional electrode 474, through the stimulation members 414 and theelongate body 402, to the first end 404. The conductive elements 476terminate at a connector port, where each of the conductive elements 420and 476 can be releasably coupled to the stimulation system, for exampleas discussed herein. In some examples, the conductive elements 420 maybe non-releasably or permanently coupled to the stimulation system. Thestimulation system can be used to provide stimulation electrical energythat is conducted through the conductive elements 420, 476 tocombinations of at least one of the additional electrodes 474 and/or atleast one of the electrodes 418.

FIG. 4C is a side perspective view of an example of a portion 401 of acatheter. The portion 401 may be used with the catheter 300, 400, othercatheters described herein, and the like. The portion 401 comprises aplurality of elongate splines 471. The splines 471 may compriseresilient or shape memory material configured to form an expanded shape(e.g., the conical shape shown in FIG. 4C or another shape) when notconfined, for example in a catheter body. The portion 401 comprises astructure 472 extending between at least two of the elongate splines471. One or more electrodes 474 can be coupled to the structure 472(e.g., by adhering, soldering, welding, tying, combinations thereof, andthe like). The electrodes 474 may be aligned with the splines 471,between the splines 471, and combinations thereof. For example, in theportion 401, the structure 472 is over three circumferentially-offsetsplines 471. The middle set of four electrodes 474 is aligned with amiddle spline 471 and the outer sets of four electrodes 474 are betweenthe middle spline 471 and the outer splines 471, forming a 3×4 array ormatrix of electrodes 474. In examples comprising a plurality ofelectrodes 474, the electrodes 474 can be aligned (e.g., as illustratedin FIG. 4C) in a two-dimensional pattern, in a three-dimensional pattern(e.g., accounting for the curvature of the expanded shape of the splines471), or scattered without a specific order. The electrodes 474 canthemselves form an electrode array, or together with other electrodes(e.g., on the splines 471) may form an electrode array.

The structure 472 can comprise a woven or knitted mesh or membrane. Thestructure may comprise insulative material, for example medical gradepolyurethanes, such as polyester-based polyurethanes, polyether-basedpolyurethanes, and polycarbonate-based polyurethanes; polyamides,polyamide block copolymers, polyolefins such as polyethylene (e.g.,high-density polyethylene, low-density polyethylene), and polyimides,and the like.

In some examples, the structure 472 may be slid over the splines 471.For example, lateral edges or medial sections of the structure 472 mayinclude loops configured to be slid over the splines 471. Althoughillustrated in FIG. 4C as arcuate over part of the circumference of theportion 401, the structure 472 may be arcuate around an entirecircumference of the portion 401. In certain such examples, thestructure 472 can be slid over the splines 471 as a telescoping tube.The structure 472 may be coupled to the splines 471 and/or tethered to acatheter.

In some examples, a plurality of structures 472 may be used. Forexample, a plurality of partially arcuate structures may be positionedaround the splines 471 (e.g., in different circumferential positions, inoverlapping circumferential positions, and/or in the samecircumferential position (e.g., with different electrode 474 patterns)).For another example, a structure 472 may be substantially tubular suchthat it can be slid over a single spline, and a plurality of suchstructures 472 can be used on different splines or even the same spline.

Forming electrodes on a structure 472 can aid in manufacturing. Forexample, the electrodes 474 can be coupled to the structure 472independent of forming the splines 471 (e.g., as opposed to formingelectrodes in or on the splines 471). In some examples, the electrodes474 can be formed on the structure 472, for example like flex circuitmanufacturing. The structure 472 may also help to position conductiveelements electrically connecting the electrodes 474 to a stimulationsystem.

The catheter 400 optionally comprises an anchor wire 478 extendinglongitudinally through the stimulation member elongate body 422. Theelongate body 402 and the member elongate body 422 include a surface atleast partially defining a lumen having a first opening at the proximalend 404 and a second opening at or adjacent to the distal end 424 of thestimulation member elongate body 422. The anchor wire 478 freely passesthrough the lumen, with a first end 480 extending from the elongate body422 at the proximal end 404 of the elongate body 402 and a second end482 comprising an anchoring structure (e.g., a barb) that extends fromthe second opening at or adjacent to the distal end 424 of thestimulation member elongate body 422. The anchor wire 478 can be advancethrough the lumen (e.g., longitudinal force can be applied to the firstend 480 of the anchor wire 478) to extend the anchoring structure awayfrom the stimulation member elongate body 414. The anchor member 436 mayhelp to anchor the catheter 400 in the subject, for example as discussedherein. The anchor wire 478 can also or alternatively be used to helpsecure the catheter 400 in the subject at a desired location. One ormore of the anchor wire 478 and the associated structures can also beincluded with the catheter 300. Optionally, the anchor wire 478 can beconfigured and used as an electrode with the stimulation system of thepresent disclosure. For example, the anchor wire 478 can be configuredas an anode and one or more of the electrodes 418, 474 can be configuredas a cathode and/or an anode, and/or the anchor wire 478 can beconfigured as a cathode and one or more of the electrodes 418, 474 canbe configured as an anode and/or a cathode.

FIG. 4A also illustrates a pulmonary artery catheter 444 (partiallyshown to show detail of catheter 400), for example similar to thepulmonary artery catheter 344 discussed herein. A catheter systemcomprising the pulmonary artery catheter 444 can be used to position thecatheter 400 in the main pulmonary artery and/or one of the pulmonaryarteries of the patient, for example as described herein. The pulmonaryartery catheter 444 with the catheter 400 positioned within the lumen454 is introduced into vasculature through a percutaneous incision andguided to the right ventricle. The balloon 458 is inflated through theinflation lumen 466, allowing the pulmonary artery catheter 444 and thecatheter 400 to be carried by the flow of blood from the right ventricleto the main pulmonary artery or one of the pulmonary arteries.

The catheter system shown in FIGS. 4A and 4B comprises an optionalpositioning gauge 484. The positioning gauge 484 includes an elongategauge body 486 having a first end 488 and a bumper end 490 distal to thefirst end 488. The elongate gauge body 486 can be moved longitudinallywithin a lumen 492 at least partially defined by a surface that extendsthrough the elongate body 402 from its first end 404 through the secondend 406. The bumper end 490 can have a shape with an example surfacearea being no less than a surface area of the distal end 406 of theelongate body 402 taken perpendicularly to the longitudinal axis 408.The elongate gauge body 486 extends through the lumen 492 to positionthe bumper end 490 distal to the second end 406 of the elongate body402. The first end 488 of the position gauge 484 extends proximally fromthe first end 404 of the elongate body 402. The elongate gauge body 486may include a marking 494 that indicates a length between the second end406 of the elongate body 402 and the bumper end 490 of the positiongauge 484.

During navigating the catheter 400, the bumper end 490 of thepositioning gauge 484 may be approximately longitudinally even with thedistal end 424 of the stimulation member elongate body 422, the distalend 442 of the anchor member 436, and the distal end 450 of thepulmonary artery catheter 444 (e.g., the elongate body 402, the anchormember 436, and the elongate stimulation members 414 are positioned inthe lumen 456 of the pulmonary artery catheter 444). In thisconfiguration, the catheter system can be advance along the mainpulmonary artery until the bumper end 490 of the positioning gauge 484contacts the top of the main pulmonary artery (e.g., a location distalto the pulmonary valve and adjacent to both the pulmonary arteries). Thecatheter system can be distally advanced when beyond the pulmonary valvewith the balloon 458 in the inflated or deflated state.

Once the bumper end 490 contacts the top of the main pulmonary artery,the pulmonary artery catheter 444 (with the catheter 400 positioned inthe lumen 456) can be moved relative the bumper end 490 (e.g., thepulmonary artery catheter 444 and the catheter 400 can be moved awayfrom the bumper end 490). As the pulmonary artery catheter 444 and thecatheter 400 move relative to the bumper end 490, the markings 494 onthe elongate gauge body 486 can be used to indicate a length between thedistal end 224 of the stimulation member elongate body 422, the distalend 442 of the anchor member 436, the distal end 450 of the pulmonaryartery catheter 444, and the bumper end 490 of the position gauge 484.The distance between the markings 494 can be in certain units (e.g.,millimeters, inches, etc.), which can allow the length the between thedistal end 424 of the stimulation member elongate body 422, the distalend 442 of the anchor member 436, and the distal end 450 of thepulmonary artery catheter 444 to be determined. Once a length that isdesired is achieved, the pulmonary artery catheter 444 can be movedrelative the catheter 400 so as to deploy the anchor member 436 and theelongate stimulation members 414 with the electrodes 418 within the mainpulmonary artery or one of the pulmonary arteries.

The ability to measure distance from the top of the main pulmonaryartery may be helpful in placing the electrodes 418 in a desiredlocation in the main pulmonary artery or one of the pulmonary arteries.For example, the distal end 424 of the stimulation member elongate body422 and the distal end 442 of the anchor member 436 can be positioned atthe desired distance from the top of the main pulmonary artery using themarkings 494 on the peripheral surface of the positioning gauge 484. Thewires 426, 440 can be used to impart curves into the elongatestimulation members 414 and the anchor member 436, respectively. Usingthe wires 426 and the wire 440, the elongate stimulation members 414 andthe anchor member 436 can be provided with curves of sufficient size tocontact the anterior surface of the main pulmonary artery and bring theelectrodes 418 into contact with the luminal surface of the mainpulmonary artery. The anchor member 436 can bias and help to anchor theelectrodes 418 along the vessel surface (e.g., along the posteriorsurface of the main pulmonary artery). Optionally, the anchor member 436can be configured to include one or more electrodes 418, for example asdiscussed herein.

Due to its adjustable nature (e.g., changing apposition pressuredepending on the amount of longitudinal force or pressure is applied tothe wire 440), the anchor member 436 can be used to bring the electrodes418 into contact with the luminal surface of the main pulmonary arteryor one of the pulmonary arteries under a variety of pressures. Forexample, the anchor member 436 can bring the electrodes 418 into contactwith the luminal surface of the main pulmonary artery or one of thepulmonary arteries under a first pressure. Using stimulation electricalenergy from the stimulation system, electrical energy can be deliveredacross combinations of two or more of the electrodes 418, 474. Thesubject's cardiac response to the stimulation electrical energy can thenbe monitored and recorded for comparison to subsequent tests. Ifdesired, the longitudinal pressure applied to the anchor member 436 canbe reduced, and the elongate body 402 can be rotated in either aclockwise or counter-clockwise direction and/or lengthwise relative tothe top of the main pulmonary artery or one of the pulmonary arteries toreposition the electrodes 418 in contact with the luminal surface of themain pulmonary artery or one of the pulmonary arteries. The stimulationsystem can again be used to deliver stimulation electrical energy acrosscombinations of two or more of the electrodes 418, 474. The subject'scardiac response to this subsequent test can then be monitored andrecorded for comparison to previous and subsequent tests. In this way, apreferred location for the position of the electrodes 418 along theluminal surface of the main pulmonary artery or one of the pulmonaryarteries can be identified. Once identified, the wire 440 can be used toincrease the pressure applied by the anchor member 436, thereby helpingto better anchor the catheter 400 in the patient.

Referring now to FIG. 5, an example of a catheter 500 is shown, wherethe catheter 500 may include the structures and features of the othercatheters discussed herein. As illustrated, the catheter 500 includes anelongate body 502 having a first end 504 and a second end 506 distalfrom the first end 504. As illustrated, the elongate body 502 includesan elongate radial axis 508 that extends through the first end 504 andthe second end 506 of the elongate body 502. As illustrated, a firstplane 510 extends through the elongate radial axis 508 over the lengthof the elongate body 502. A second plane 512 perpendicularly intersectsthe first plane 510 along the longitudinal axis 508 of the elongate body502. The first plane 510 and the second plane 512 divide a first volume516 into a first quadrant volume 532 and a second quadrant volume 534.The catheter 500 further includes at least two elongate stimulationmembers 514, as discussed herein, that extend from the elongate body502. Each of the at least two elongate stimulation members 514-1 and514-2 curves into a first volume 516 defined at least in part by thefirst plane 510. For example, the at least two elongate stimulationmembers 514 may extend from approximately the second end 506 of theelongate body 502 into the first volume 516.

FIG. 5 also illustrates at least one electrode 518 on each of the atleast two elongate stimulation members 514. The at least one electrode518 on each of the elongate stimulation members 514 form an electrodearray in the first volume 516. The at least one electrode 518 on each ofthe elongate stimulation members 514 may be electrically isolated fromone another and/or may comprise an electrically insulating material. Thecatheter 500 also includes conductive elements 520 that extend throughand/or along each of the elongate stimulation members 514. As discussedherein, the conductive elements 520 can conduct electrical current tocombinations of two or more of the electrodes 518. The conductiveelements 520 may be electrically isolated from each other. Theconductive elements 520 may terminate at a connector port, where each ofthe conductive elements 520 can be releasably coupled to a stimulationsystem, for example as discussed herein. In some examples, theconductive elements 520 are permanently coupled to the stimulationsystem (e.g., not releasably coupled). The stimulation system can beused to provide stimulation electrical energy that is conducted throughthe conductive elements 520 and delivered across combinations of theelectrodes 518 in the electrode array.

Each of the at least two elongate stimulation members 514 includes astimulation member elongate body 522 having a distal end 524 that canmove relative to each other. In other words, the distal ends 524 of eachof the stimulation member elongate bodies 522 are free of each other. Asillustrated in FIG. 5, the at least two elongate stimulation members 514curve only in the first volume 516 defined at least in part by the firstplane 510. FIG. 5 also illustrates a second volume 530 defined at leastin part by the first plane 510 (being opposite the first volume 516)that contains no electrodes. FIG. 5 also illustrates an example in whichthe at least two elongate stimulation members 514 include a firstelongate stimulation member 514-1 and a second elongate stimulationmember 514-2, where the first elongate stimulation member 514-1 curvesinto the first quadrant volume 532 and the second elongate stimulationmember 514-2 curves into the second quadrant volume 534, as previouslydiscussed herein. The catheter 500 also includes an anchor member 536that extends from the elongate body 502 into the second volume 530. Asillustrated, the anchor member 536 does not include an electrode. Theanchor member 536 includes an elongate body 538 as previously discussedin connection with previous figures. Optionally, the anchor member 536can be configured to include one or more of the electrodes 518 asdiscussed herein.

Each of the at least two elongate stimulation members 514 and the anchormember 536 can also include a wire 566 extending longitudinally throughthe stimulation member elongate body 522 and the elongate body 538,respectively. The wire 566 can provide each of the at least two elongatestimulation members 514 and the anchor member 536 with a predefinedshape. For example, the wire 566 in each of the at least two elongatestimulation members 514 and the anchor member 536 can have a coil orhelical configuration that imparts a curve to the stimulation memberelongate body 522 and the elongate body 538, respectively. The wire 566can also impart stiffness to the stimulation member elongate body 522that is sufficient to maintain the predefined shape under the conditionswithin the vasculature of the patient. So, for example, the wire 566provides sufficient stiffness and flexibility to the stimulation memberelongate body 522 to elastically return the least two elongatestimulation members 514 to their curved configuration when placed in thevasculature of a patient.

The wire 566 can be formed of a variety of metals or metal alloys.Examples of such metals or metal alloys include surgical grade stainlesssteel, such as austenitic 516 stainless among others, and the nickel andtitanium alloy known as Nitinol. Other metals and/or metal alloys canalso be used as desired and/or required. The predefined shape may beadapted to conform to a particular anatomical structure (e.g., the rightor left pulmonary artery or other portion of a pulmonary trunk).

The at least two elongate stimulation members 514 can also include ananchor wire 544, as discussed herein, extending longitudinally through alumen in the stimulation member elongate body 522 and the elongate body502. The anchor wire 544 includes a first end 546 extending from theelongate body 502 and a second end 548 having an anchoring structure(e.g., a barb). The anchor wire 544 can be advanced through the lumen(e.g, longitudinal force can be applied to the first end 546 of theanchor wire 544) to extend the anchoring structure away from thestimulation member elongate body 514. In addition to the use of theanchor member 536 in helping to better anchor the catheter 500 in thepatient, as discussed herein, the anchor wire 544 can also be used tohelp secure the catheter 500 in the patient at the desired location.Optionally, the anchor wire 544 can be configured and used as anelectrode with the stimulation system of the present disclosure.

In accordance with several examples, the catheter 500 further includes apulmonary artery catheter 591, as discussed herein. As illustrated, thepulmonary artery catheter 591 (partially shown to show detail ofcatheter 500) that can be used with catheter 500 to provide for acatheter system. The pulmonary artery catheter 591 includes an elongatecatheter body 5100 with a first end 5102, a second end 5104, aperipheral surface 5106 and an interior surface 5108, opposite theperipheral surface 5106. The interior surface 5108 defines a lumen 5110that extends between the first end 5102 and the second end 5104 of theelongate catheter body 5100. The lumen 5110 is of a sufficient size andshape to house at least a portion of the catheter 500 inside the lumen5110 during delivery of the catheter 500. For example, the anchor member536 and the at least two elongate stimulation members 514, along with aleast a portion of the elongate body 502, can be positioned within thelumen 5110 during delivery. The anchor member 536, the at least twoelongate stimulation members 514 and at least a portion of the elongatebody 502 can be deployed from the distal end 5104 of the pulmonaryartery catheter 591 during the delivery and implantation of the catheter500.

The pulmonary artery catheter 591 can further include an inflatableballoon 5112 on the peripheral surface 5106 of the elongate catheterbody 5100. The inflatable balloon 5112 includes a balloon wall 5114 withan interior surface 5116 that, along with a portion of the peripheralsurface 5106 of the elongate catheter body 5100, defines a fluid tightvolume 5118. The pulmonary artery catheter 591 further includes aninflation lumen 5120 that extends through the elongate catheter body5100, where the inflation lumen 5120 has a first opening 5122 into thefluid tight volume 5118 of the inflatable balloon 5112 and a secondopening 5124 proximal to the first opening 5122 to allow for a fluid tomove in the fluid tight volume 5118 to inflate and deflate the balloon5112, as discussed herein. The catheter system shown in FIG. 5 can beused, for example, to position the catheter 500 in the main pulmonaryartery 202 and/or one or both of the pulmonary arteries 206, 208 of thepatient, for example as described herein. The at least two elongatestimulation members 514 and the anchor member 536 can be repositionedwithin the lumen 5110 of the pulmonary artery catheter 591 by moving theelongate catheter body 5100 relative to the elongate body 502 back overthe at least two elongate stimulation members 514 and the anchor member536. The catheter system illustrated in FIG. 5 can optionally includethe positioning gauge, as discussed in connection with FIGS. 4A and 4B,for example.

Referring now to FIG. 6, another example of a catheter 600 is shown. Asillustrated, the catheter 600 includes an elongate body 602 having afirst end 604 and a second end 606 distal from the first end 604. Asillustrated, the elongate body 602 includes an elongate radial axis 608that extends through the first end 604 and the second end 606 of theelongate body 602. As illustrated, a first plane 610 extends through theelongate radial axis 608 over the length of the elongate body 602. Asecond plane 612 perpendicularly intersects the first plane 610 alongthe longitudinal axis 608 of the elongate body 602. The first plane 610and the second plane 612 divide a first volume 616 into a first quadrantvolume 632 and a second quadrant volume 634. The catheter 600 includesat least two elongate stimulation members 614 that extend from theelongate body 602. Each of the at least two elongate stimulation members614-1 and 614-2 curves into a first volume 616 defined at least in partby the first plane 610. For example, the at least two elongatestimulation members 614 extend from approximately the second end 606 ofthe elongate body 602 into the first volume 616.

FIG. 6 also illustrates at least one electrode 618 on each of the atleast two elongate stimulation members 614. Multiple electrodes 618 onthe elongate stimulation members 614 may form an electrode array in thefirst volume 616. The catheter 600 also includes conductive elements 620that extend through and/or along each of the elongate stimulationmembers 614. As discussed previously, the conductive elements 620 canconduct electrical current to combinations of two or more of theelectrodes 618.

Each of the at least two elongate stimulation members 614 includes astimulation member elongate body 622 each having a distal end 624 thatextends from the elongate body 602. In some examples (such asillustrated in FIG. 6), the at least two elongate stimulation members614 curve only in the first volume 616 defined at least in part by thefirst plane 610. FIG. 6 also illustrates a second volume 630 defined atleast in part by the first plane 610 (being opposite the first volume616) that contains no electrodes. FIG. 6 further illustrates an examplein which the at least two elongate stimulation members 614 include afirst elongate stimulation member 614-1 and a second elongatestimulation member 614-2, where the first elongate stimulation member614-1 curves into the first quadrant volume 632 and the second elongatestimulation member 614-2 curves into the second quadrant volume 634,such as previously discussed herein. The catheter 600 also includes ananchor member 636 that extends from the elongate body 602 into thesecond volume 630. As illustrated, the anchor member 636 does notinclude an electrode. The anchor member 636 includes an elongate body638 such as previously discussed. Optionally, the anchor member 636 canbe configured to include one or more of the electrodes 618.

Each of the at least two elongate stimulation members 614 and the anchormember 636 can also include a wire 666 extending longitudinally throughand/or along the stimulation member elongate body 622 and the elongatebody 638, respectively. The wire 666 can provide each of the at leasttwo elongate stimulation members 614 and the anchor member 636 with apredefined shape. For example, the wire 666 in each of the at least twoelongate stimulation members 614 and the anchor member 636 can have acoil or helical configuration that imparts a curve to the stimulationmember elongate body 622 and the elongate body 638, respectively. Thewire 666 can also impart stiffness to the stimulation member elongatebody 622 that is sufficient to maintain the predefined shape under theconditions within the vasculature of the patient. So, for example, thewire 666 can provide sufficient stiffness and flexibility to thestimulation member elongate body 622 to elastically return the least twoelongate stimulation members 614 to their curved configuration whenplaced in the vasculature of a patient. The wire 666 can be formed of avariety of metals or metal alloys such as those as discussed herein inconnection with other examples.

The at least two elongate stimulation members 614 can also include ananchor wire 644 extending longitudinally through and/or along thestimulation member elongate body 622. The anchor wire 644 includes afirst end 646 extending from the elongate body 602 and a second end 648having an anchoring structure (e.g., a barb). Longitudinal force appliedto the first end 646 of the anchor wire 644 advances the anchor wire 644through the stimulation member elongate body 614 to extend the anchoringstructure away from the stimulation member elongate body 614.Optionally, the anchor wire 644 can be configured and used as anelectrode with the stimulation system of the present disclosure.

The catheter 600 further includes a pulmonary artery catheter 691, aspreviously discussed herein. As illustrated, the pulmonary arterycatheter 691 (partially shown to show detail of catheter 600) can beused with the catheter 600 to provide a catheter system. The pulmonaryartery catheter 691 includes an elongate catheter body 670 with a firstend 680, a second end 682, a peripheral surface 676 and an interiorsurface 672, opposite the peripheral surface 676. The interior surface672 defines a lumen 674 that extends between the first end 680 and thesecond end 682 of the elongate catheter body 670. The lumen 674 may beof a sufficient size and shape to house at least a portion of thecatheter 600 inside the lumen 674 during delivery of the catheter 600.For example, the anchor member 636 and the at least two elongatestimulation members 614, along with a least a portion of the elongatebody 602, can be positioned within the lumen 674. The anchor member 636,the at least two elongate stimulation members 614 and at least a portionof the elongate body 602 can be deployed from the distal end 682 of thepulmonary artery catheter 691 during the delivery and implantation ofthe catheter 600.

The pulmonary artery catheter 691 can further include an inflatableballoon 668 on the peripheral surface 676 of the elongate catheter body670. The inflatable balloon 668 has a balloon wall 688 with an interiorsurface 690 that, along with a portion of the peripheral surface 676 ofthe elongate catheter body 670 defines a fluid tight volume 692. Thepulmonary artery catheter 691 further includes an inflation lumen 694that extends through the elongate catheter body 670, where the inflationlumen 694 has a first opening 696 into the fluid tight volume 692 of theinflatable balloon 668 and a second opening 698 proximal to the firstopening 696 to allow for a fluid to move in the fluid tight volume 692to inflate and deflate the balloon 668, for example as previouslydiscussed herein. The catheter system shown in FIG. 6 can be used toposition the catheter 600 in the main pulmonary artery and/or one orboth of the pulmonary arteries of the patient, for example as describedherein. The at least two elongate stimulation members 614 and the anchormember 636 can be repositioned within the lumen 694 of the pulmonaryartery catheter 691 by moving the elongate catheter body 670 relativethe elongate body 602 back over the at least two elongate stimulationmembers 614 and the anchor member 636. The catheter system illustratedin FIG. 6 can optionally include the positioning gauge, as discussed inconnection with FIGS. 4A and 4B, for example.

Referring now to FIGS. 7A and 7B, there is shown alternative examples ofa pulmonary artery catheter 791 that can be used with any of thecatheters described herein (e.g., catheter 300, 400, 500 or 600). Asillustrated, the pulmonary artery catheter 791 includes an elongatecatheter body 7100 with a first end 7102, a second end 7104, aperipheral surface 7106 and an interior surface 7108, opposite theperipheral surface 7106. The interior surface 7108 defines a lumen 7110that extends between the first end 7102 and the second end 7104 of theelongate catheter body 7100. The lumen 7110 is of a sufficient size andshape to house at least a portion of the catheter (e.g., catheter 300,400, 500 or 600) inside the lumen 7110 during delivery of the catheter.For example, the anchor member and the at least two elongate stimulationmembers, along with a least a portion of the elongate body, can bepositioned within the lumen 7110. The anchor member, the at least twoelongate stimulation members and at least a portion of the elongate bodycan be deployed from the distal end 7104 of the pulmonary arterycatheter 791 during the delivery and implantation of the catheter (e.g.,catheter 300, 400, 500 or 600).

The pulmonary artery catheter 791 includes an inflatable balloon 7112.As illustrated, the inflatable balloon 7112 is positioned on an elongateinflation catheter body 7300 that passes through a balloon lumen 7302.The balloon lumen 7302 is defined by lumen surface 7304 that can extendfrom the first end 7102 through the second end 7104 of the elongatecatheter body 7100. The balloon lumen 7302 has a cross-sectionaldimension that allows the elongate inflation catheter body 7300 tolongitudinally move within the balloon lumen 7302. As such, theinflatable balloon 7112 can be moved relative to the distal end 7104 ofthe pulmonary artery catheter 791.

The inflatable balloon 7112 has a balloon wall 7114 with an interiorsurface 7116 that along with a portion of a peripheral surface 7106 ofthe elongate inflation catheter body 7300 defines a fluid tight volume7116. The elongate inflation catheter body 7300 further includes aninflation lumen 7120 that extends through the elongate inflationcatheter body 7300, where the inflation lumen 7120 has a first opening7122 into the fluid tight volume 7116 of the inflatable balloon 7112 anda second opening 7124 proximal to the first opening 7122 to allow for afluid to move in the fluid tight volume 7116 to inflate and deflate theballoon 7112. A syringe, or other known devices, containing the fluid(e.g., saline or a gas (e.g., oxygen)) can be used to inflate anddeflate the balloon 7112. The cross-sectional dimension of the balloonlumen 7302 is also sufficient to allow the inflatable balloon 7112 inits fully deflated state to be housed within the lumen 7302. Theinflatable balloon 7112 along with at least a portion of the elongateinflation catheter body 7300 can be extended from the second end 7104when the inflatable balloon 7112 is to be inflated.

FIG. 7B illustrates an alternative example of the pulmonary arterycatheter 791 that can be used with any of the catheters (e.g., catheters300, 400, 500, or 600) according to the present disclosure. As with thepulmonary artery catheter 791 illustrated in FIG. 7A, the pulmonaryartery catheter 791 includes an elongate catheter body 7100 with a firstend 7102, a second end 7104, a peripheral surface 7106 and an interiorsurface, opposite the peripheral surface 7106. The interior surfacedefines the lumen 7110 that extends between the first end 7102 and thesecond end 7104 of the elongate catheter body 7100. The lumen 7110 is ofa sufficient size and shape to house at least a portion of the catheter(e.g., catheter 300, 400, 500, or 600) inside the lumen 7110 duringdelivery of the catheter. For example, the anchor member and the atleast two elongate stimulation members, along with a least a portion ofthe elongate body, can be positioned within the lumen 7110 (the exampleillustrated in FIG. 7B has the catheter (e.g., catheter 300, 400, 500,or 600) fully inside the lumen 7110). The anchor member, the at leasttwo elongate stimulation members and at least a portion of the elongatebody can be deployed from the distal end 7104 of the pulmonary arterycatheter 791 during the delivery and implantation of the catheter (e.g.,catheter 300, 400, 500, or 600).

The pulmonary artery catheter 791 illustrated in FIG. 7B includes twoinflatable balloons 7112 (shown as 7112-1 and 7112-2 in FIG. 7B). Asillustrated, each of the inflatable balloons 7112-1 and 7112-2 arepositioned on separate elongate inflation catheter bodies 7300-1 and7300-2, where each of the elongate inflation catheter bodies 7300-1 and7300-2 pass through a balloon lumen 7302-1 and 7302-2, respectively. Asillustrated, each balloon lumen 7302-1 and 7302-2 is defined by a lumensurface 7304-1 and 7304-2, respectively, which can extend from the firstend 7102 through the second end 7104 of the elongate catheter body 7100.The balloon lumens 7302-1 and 7302-2 each have a cross-sectionaldimension that allows the elongate inflation catheter body 7300-1 and7300-2 to longitudinally move within their respective balloon lumen7302-1 and 7302-2. As such, each of the inflatable balloons 7112-1and/or 7112-2 can be independently moved relative to the distal end 7104of the pulmonary artery catheter 791. As with FIG. 7A, thecross-sectional dimension of each balloon lumen 7302-1 and 7302-2 may besufficient to allow each respective inflatable balloon 7112-1 and 7112-2in its fully deflated state to be housed within each respective balloonlumen 7302-1 and 7302-2. Each inflatable balloon 7112-1 and 7112-2,along with at least a portion of the elongate inflation catheter body7300-1 and 7300-2, can independently be extended from the second end7104 when the inflatable balloon 7112-1 and/or 7112-2 is to be inflated.

Each of the inflatable balloons 7112-1 and 7112-2 has a balloon wall7114-1 and 7114-2 with an interior surface 7116-1 and 7116-2,respectively, which along with a portion of a peripheral surface 7106 ofthe elongate inflation catheter body 7300-1 and 7300-2 define a fluidtight volume 7118-1 and 7118-2, respectively. The elongate inflationcatheter body 7300 further includes an inflation lumen 7120-1 and 7120-2that extends through the elongate inflation catheter body 7300-1 and7300-2, respectively, where the inflation lumen 7120-1, 7120-2 has afirst opening 7122-1, 7122-2 into the fluid tight volume 7118-1, 7118-2of the inflatable balloon 7112-1 and 7112-2 and a second opening 7124-1and 7124-2 proximal to the first opening 7122-1 and 7122-2 to allow fora fluid (e.g., liquid or gas) to move in and out of the fluid tightvolume 7118-1 and 7118-2 to inflate and deflate the balloon 7112-1 and7112-2. Each of the inflatable balloons 7112-1 and 7112-2 can beindependently moved relative to the second end 7104 of the elongate body7100 as well as independently inflated, as discussed elsewhere herein.

The pulmonary artery catheter 791 further includes a positioning gauge752. The positioning gauge 752 includes an elongate gauge body 754 witha first end 756 and a bumper end 758 distal to the first end 756. Theelongate gauge body 754 can be moved longitudinally within a lumen 750defined by a surface that extends through the elongate catheter body7100. The elongate gauge body 754 extends through the lumen 750 of theelongate catheter body 7100 to position the bumper end 758 beyond thesecond end 7104 of the elongate catheter body 7100. The first end 756 ofthe position gauge 752 extends from the first end 7102 of the elongatecatheter body 7100, where the elongate gauge body 754 includes a markingthat indicates a length between the second end 7104 of the elongatecatheter body 7100 and the bumper end 758 of the position gauge 752.

The pulmonary artery catheter 791 can also include a first anchor 729that extends laterally from the peripheral surface 7106 of the elongatecatheter body 7100. As illustrated, the first anchor 729 has struts 731that form an open framework. The struts 731 have a peripheral surface733 having a largest outer dimension that allows the first anchor 729(when deployed) to engage a surface of the main pulmonary artery and/orone or both of the pulmonary arteries. A sheath can cover and hold thefirst anchor 729 in an undeployed state as the pulmonary artery catheter791 and the catheter (e.g., catheter 300, 400, 500, or 600) are beingintroduced into the patient.

The catheter system shown in FIGS. 7A and 7B can be used to position acatheter (e.g., catheter 300, 400, 500, and/or 600) in the mainpulmonary artery and/or one or both of the right and left pulmonaryarteries of the patient, for example as described herein. To accomplishthis, the pulmonary artery catheter 791 with the catheter positionedwithin the lumen 7110 is introduced into the vasculature through apercutaneous incision, and guided to the right ventricle (e.g., using aSwan-Ganz approach through an incision in the neck). For the cathetersystem of FIG. 7A, the balloon 7112 is inflated, as described, to allowthe pulmonary artery catheter 791 and the catheter to be carried by theflow of blood from the right ventricle to the main pulmonary artery orone of the right or left pulmonary arteries. Once the pulmonary arterycatheter 791 and the catheter (e.g., catheter 300, 400, 500, and/or 600)have been carried from the right ventricle into the main pulmonaryartery or one of the right or left pulmonary arteries the sheath can beretracted, thereby allowing the first anchor 729 to deploy within themain pulmonary artery. The first anchor 729 can be brought back into itsundeployed state by positioning the sheath (e.g., advancing the sheath)back over the first anchor 729.

With the first anchor 729 in its deployed position, the positioninggauge 752 can be used to determine a length between the second end 7104of the elongate catheter body 7100 and the top of the main pulmonaryartery (e.g., a location distal to the pulmonary valve and adjacent toboth the right and left pulmonary arteries). Knowing this length, thecatheter (e.g., catheter 300, 400, 500, 600) can be advanced from thelumen 7110 of the elongate catheter body 7100 to a location between thesecond end 7104 of the elongate catheter body 7100 and the top of themain pulmonary artery. This location can be determined, for example,using markings (e.g., markings providing a length in, for example,millimeters) on a portion of the elongate body of the catheter thatextends proximally from the first end 7102 of the elongate catheter body7100.

Referring now to FIGS. 8A through 8D, there is shown an additionalexample of a catheter 800 according to the present disclosure. Thecatheter 800 includes an elongate catheter body 801 having a first end803 and a second end 805. The elongate catheter body 801 also includes aperipheral surface 807 and an interior surface 809 defining an inflationlumen 811 (shown with a broken line) that extends at least partiallybetween the first end 803 and the second end 805 of the elongatecatheter body 801.

The catheter 800 includes an inflatable balloon 813 on the peripheralsurface 807 of the elongate catheter body 801. The inflatable balloon813 includes a balloon wall 815 with an interior surface 817 that, alongwith a portion of the peripheral surface 807 of the elongate catheterbody 801, defines a fluid tight volume 819. The inflation lumen 811includes a first opening 821 into the fluid tight volume 819 of theinflatable balloon 813 and a second opening 823 proximal to the firstopening 821 to allow for a fluid to move in and out of the volume 819 toinflate and deflate the balloon 813.

The catheter 800 further includes a plurality of electrodes 825positioned along the peripheral surface 807 of the elongate catheterbody 801. The plurality of electrodes 825 is located between theinflatable balloon 813 and the first end 803 of the elongate catheterbody 801. Conductive elements 827 extend through the elongate catheterbody 801, where the conductive elements 827 conduct electrical currentto combinations of two or more of the plurality of electrodes 825.

The catheter 800 further includes a first anchor 829 that extendslaterally from the peripheral surface 807 of the elongate body 801, thefirst anchor 829 having struts 831 forming an open framework. In theillustrated example, the struts 831 have a peripheral surface 833 havinga largest outer dimension greater than the largest outer dimension ofthe inflatable balloon 813 (e.g., its largest diameter). As illustrated,the first anchor 829 has a center point 835 relative to the peripheralsurface 833 that is eccentric relative to a center point 837 of theelongate catheter body 801 relative to the peripheral surface 807.

FIGS. 8A and 8B both show the first anchor 829. FIG. 8A shows the firstanchor 829 positioned between the inflatable balloon 813 and theplurality of electrodes 825 positioned along the peripheral surface 807of the elongate catheter body 801. FIG. 8B shows the first anchor 829positioned between the plurality of electrodes 825 positioned along theperipheral surface 807 of the elongate catheter body 801 and the firstend 803 of the elongate catheter body 801.

For the catheter 800 shown in FIG. 8A, a portion 839 of the elongatecatheter body 801 that includes the plurality of electrodes 825 maycurve in a predefined radial direction when placed under longitudinalcompression. To achieve the curving of this portion 839 that includesthe plurality of electrodes 825, the elongate catheter body 801 can bepre-stressed and/or the wall can have thicknesses that allow for theelongate catheter body 801 to curve in the predefined radial directionwhen placed under longitudinal compression. In addition, oralternatively, structures such as coils or a helix of wire havingdifferent turns per unit length can be located within the elongatecatheter body 801 in the portion 839. One or more of these structurescan be used to allow the longitudinal compression to create the curve inthe predefined radial direction in the portion 839. To achieve thelongitudinal compression, the first anchor 829 can be deployed in thevasculature of the patient (e.g., in the pulmonary artery), where thefirst anchor 829 provides a location or point of resistance against thelongitudinal movement of the elongate body 801. As such, this allows acompressive force to be generated in the elongate catheter body 801sufficient to cause the portion 839 of the elongate catheter body 801along which the plurality of electrodes 825 are present to curve in thepredefined radial direction.

FIG. 8C provides an illustration of the portion 839 of the elongatecatheter body 801 curved in a predefined radial direction when placedunder longitudinal compression. The catheter 800 illustrated in FIG. 8Cis representative of the catheter shown in FIG. 8A and is describedherein. As illustrated, the catheter 800 has been at least partiallypositioned within the main pulmonary artery 8500 of a patient's heart(the catheter 800 can also be at least partially positioned within theright pulmonary artery 8504 as illustrated), where the balloon 813 andthe first anchor 829 are located in the lumen of the left pulmonaryartery 8502. From this position, a compressive force applied to theelongate catheter body 801 can cause the portion 839 of the elongatecatheter body 801 with the plurality of electrodes 825 to curve in thepredefined radial direction, thereby allowing (e.g., causing) theplurality of electrodes 825 to extend towards and/or touch the luminalsurface of the main pulmonary artery 8500. In accordance with severalexamples, the plurality of electrodes 825 are brought into positionand/or contact with the luminal surface of the main pulmonary artery8500.

Providing a rotational torque at the first end 803 of the elongatecatheter body 801 can help to move the plurality of electrodes 825relative to the luminal surface, thereby allowing a professional orclinician to “sweep” the plurality of electrodes 825 into differentpositions along the luminal surface of the main pulmonary artery 8500.As discussed herein, this allows for the patient's cardiac response tothe stimulation electrical energy to be monitored and recorded at avariety of locations along the luminal surface of the main pulmonaryartery 8500. In this way, a preferred location for the position of theelectrodes 825 along the luminal surface of the main pulmonary artery8500 can be identified. In accordance with other examples, the pluralityof electrodes 825 may be brought into position and/or contact with theluminal surface of the left pulmonary artery 8502 or the right pulmonaryartery 8504 or at other locations, as desired and/or required.

Alternatively, for the catheter 800 shown in FIG. 8B, the elongatecatheter body 801 can include a second interior surface 841 defining ashaping lumen 843 that extends from the first end 803 towards the secondend 805. The catheter 800 of FIG. 8B can also include a shaping wire 845having a first end 847 and a second end 849. In one example, the shapinglumen 843 has a size (e.g., a diameter) sufficient to allow the shapingwire 845 to pass through the shaping lumen 843 with the first end 847 ofthe shaping wire 845 proximal to the first end 803 of the elongatecatheter body 801 and the second end 849 of the shaping wire 845 joinedto the elongate catheter body 801 so that the shaping wire 845 imparts acurve into the portion 839 of the elongate catheter body 801 having theplurality of electrodes 825 when tension is applied to the shaping wire845.

FIG. 8D provides an illustration of the portion 839 of the elongatecatheter body 801 curved in a predefined radial direction when using theshaping lumen and shaping wire as discussed herein (the catheter 800illustrated in FIG. 8D is the catheter shown in FIG. 8B and is describedherein). As illustrated, the catheter 800 has been at least partiallypositioned within the main pulmonary artery 8500 of a patient's heart,where the balloon 813 is located in the lumen of the left pulmonaryartery 8502 and the first anchor 829 is located in the main pulmonaryartery 8500. From this position, the shaping wire 845 can be used toimpart the curve into the portion 839 of the elongate catheter body 801having the plurality of electrodes 825 when tension is applied to theshaping wire 845, thereby allowing (e.g., causing) the plurality ofelectrodes 825 to extend towards and/or touch the luminal surface of themain pulmonary artery 8500 (the catheter 800 can also be at leastpartially positioned within the right pulmonary artery 8504 asillustrated). In accordance with several examples, the plurality ofelectrodes 825 are brought into position and/or contact with the luminalsurface of the main pulmonary artery. In accordance with other examples,the plurality of electrodes 825 may be brought into position and/orcontact with the luminal surface of the left pulmonary artery 8502 orthe right pulmonary artery 8504 or at other locations, as desired and/orrequired.

Providing a rotational torque at the first end 803 of the elongatecatheter body 801 can help to move the plurality of electrodes 825relative to the luminal surface of the main pulmonary artery 8500(and/or the right or left pulmonary artery), thereby allowing aprofessional or clinician to “sweep” the plurality of electrodes 825into different positions along the luminal surface of the main pulmonaryartery (and/or the right or left pulmonary artery), as discussed herein,so as to identify a preferred location for the position of theelectrodes 825 along the luminal surface of the main pulmonary artery(and/or the right or left pulmonary artery).

As illustrated, the catheter 800 of FIGS. 8A and 8B both include anelongate delivery sheath 851 having a lumen 853 that extends over aperipheral surface 807 of the elongate body 801. The elongate deliverysheath 851, in a first position, can have the first anchor 829positioned within the lumen 853 of the elongate delivery sheath 851. Asthe elongate delivery sheath 851 moves relative to the peripheralsurface 807 of the elongate body 801 the first anchor 829 extends fromthe peripheral surface 807 of the elongate body 801.

Referring now to FIG. 9, there is shown an additional example of acatheter 900. As described for catheter 800, catheter 900 includes anelongate catheter body 901 having a first end 903 and a second end 905,a peripheral surface 907 and an interior surface 909 defining aninflation lumen 911 that extends at least partially between the firstend 903 and the second end 905 of the elongate catheter body 901. Thecatheter 900 includes an inflatable balloon 913 on the peripheralsurface 907 of the elongate catheter body 901, the inflatable balloon913 having a balloon wall 915 with an interior surface 917 that, alongwith a portion of the peripheral surface 907 of the elongate catheterbody 901, defines a fluid tight volume 919. The inflation lumen 911includes a first opening 921 into the fluid tight volume 919 of theinflatable balloon 913 and a second opening 923 proximal to the firstopening 921 to allow for a fluid (e.g., liquid or gas) to move in andout of the volume 919 to inflate and deflate the balloon 913.

The catheter 900 includes a plurality of electrodes 925 positioned alongthe peripheral surface 907 of the elongate catheter body 901. As shown,the plurality of electrodes 925 is located between the inflatableballoon 913 and the first end 903 of the elongate catheter body 901.Conductive elements 927 extend through the elongate catheter body 901,where the conductive elements 927 conduct electrical current tocombinations of one or more of the plurality of electrodes 925.

The catheter 900 further includes a first anchor 929 and a second anchor955 that both extend laterally from the peripheral surface 907 of theelongate body 901. Both the first anchor 929 and the second anchor 955have struts 931 that form an open framework for the anchors. The struts931 have a peripheral surface 933 having a largest outer dimensiongreater than the largest outer dimension of the inflatable balloon 913(e.g., its largest diameter). As illustrated, the first anchor 929 has acenter point 935 relative to the peripheral surface 933 that iseccentric relative to a center point 937 of the elongate catheter body901 relative to the peripheral surface 907. In contrast, the secondanchor 955 has a center point 935 relative to the peripheral surface 933that is concentric relative to the center point 937 of the elongatecatheter body 901 relative to the peripheral surface 907. In someexamples, the first anchor 929 may have a center point 935 relative tothe peripheral surface 933 that is concentric relative to the centerpoint 937 of the elongate catheter body 901 relative to the peripheralsurface 907 and/or the second anchor 955 may have a center point 935relative to the peripheral surface 933 that is eccentric relative to acenter point 937 of the elongate catheter body 901 relative to theperipheral surface 907.

The catheter 900 includes an elongate delivery sheath 951 having a lumen953 that extends over a peripheral surface 907 of the elongate body 901.The elongate delivery sheath 951, in a first position, can have thefirst anchor 929 and the second anchor 955 positioned within the lumen953 of the elongate delivery sheath 951. As the elongate delivery sheath951 moves relative to the peripheral surface 907 of the elongate body901 the first anchor 929 extends from the peripheral surface 907 of theelongate body 901. As the elongate delivery sheath 951 moves furtheraway from the inflatable balloon 913 relative to the peripheral surface907, the second anchor 955 extends from the peripheral surface 907 ofthe elongate body 901.

As illustrated, the plurality of electrodes 925 are located between thefirst anchor 929 and the second anchor 955. A portion 939 of theelongate catheter body 901 that includes the plurality of electrodes 925can be made to curve in a predefined radial direction in a variety ofways. For example, the portion 939 of the elongate catheter body 901that includes the plurality of electrodes 925 can be made to curve inthe predefined radial direction when placed under longitudinalcompression (as discussed herein). As with the catheter 800, to causethe portion 939 that includes the plurality of electrodes 925 to curve,the elongate catheter body 901 can be pre-stressed and/or the wall canhave thicknesses that allow for the elongate catheter body 901 to curvein the predefined radial direction when placed under longitudinalcompression. In addition, or alternatively, structures such as coils ofa helix of wire having different turns per unit length can be locatedwithin the elongate catheter body 901 in the portion 939. One or more ofthese structures can be used to allow the longitudinal compression tocreate the curve in the predefined radial direction in the portion 939.

To achieve the longitudinal compression, the first anchor 929 can bedeployed in the vasculature of the patient, as discussed herein, wherethe first anchor 929 provides a location or point of resistance againstthe longitudinal movement of the elongate body 901. As discussed hereinfor example, this can be accomplished by moving the elongate deliverysheath 951 relative to the peripheral surface 907 of the elongate body901 so as to allow the first anchor 929 to extend from the peripheralsurface 907 of the elongate body 901. Once deployed, the first anchor929 allows a compressive force to be generated in the elongate catheterbody 901 sufficient to cause the portion 939 of the elongate catheterbody 901 along which the plurality of electrodes 925 are present tocurve in the predefined radial direction. Once the curve is formed inthe predefined radial direction, the elongate delivery sheath 951 ismoved further away from the inflatable balloon 913 relative to theperipheral surface 907 so as to allow the second anchor 955 to extendfrom the peripheral surface 907 of the elongate body 901.

Alternatively, the elongate catheter body 901 of the catheter 900 caninclude a second interior surface 941 defining a shaping lumen 943 thatextends from the first end 903 towards the second end 905. The catheter900 can also include a shaping wire 945 having a first end 947 and asecond end 949, where the shaping lumen 943 has a size (e.g., adiameter) sufficient to allow the shaping wire 945 to pass through theshaping lumen 943 with the first end 947 of the shaping wire 945proximal to the first end 903 of the elongate catheter body 901 and thesecond end 949 of the shaping wire 945 joined to the elongate catheterbody 901 so that the shaping wire 945 imparts a curve into the portion939 of the elongate catheter body 901 having the plurality of electrodes925 when tension is applied to the shaping wire 945.

Referring now to FIG. 10, there is shown an additional example of thecatheter 1000. As discussed above, catheter 1000 includes an elongatecatheter body 1001 having a first end 1003, a second end 1005, aperipheral surface 1007 and an interior surface 1009 defining aninflation lumen 1011 that extends at least partially between the firstend 1003 and the second end 1005 of the elongate catheter body 1001. Thecatheter 1000 also includes an inflatable balloon 1013 on the peripheralsurface 1007 of the elongate catheter body 1001, where the inflatableballoon 1013 has the balloon wall 1015 with an interior surface 1017that, along with a portion of the peripheral surface 1007 of theelongate catheter body 1001, defines a fluid tight volume 1019. Theinflation lumen 1011 includes a first opening 1021 into the fluid tightvolume 1019 of the inflatable balloon 1015 and a second opening 1023proximal to the first opening 1021 to allow for a fluid to move in andout of the volume 1019 to inflate and deflate the balloon 1015.

The elongate catheter body 1001 also includes a first anchor 1029 thatcan extend laterally from the peripheral surface 1007 of the elongatecatheter body 1001. As discussed herein, the first anchor 1029 includesstruts 1031 forming an open framework with a peripheral surface 1033having a largest outer dimension greater than the largest outerdimension of the inflatable balloon 1013 (e.g., its largest diameter).As illustrated, the first anchor 1029 has a center point 1035 relativeto the peripheral surface 1033 that is eccentric relative to a centerpoint 1037 of the elongate catheter body 1001 relative to the peripheralsurface 1007.

The catheter 1000 further includes an electrode catheter 1057 having anelectrode elongate body 1059 and a plurality of electrodes 1025positioned along a peripheral surface 1061 of the electrode elongatebody 1059. Conductive elements 1063 extend through and/or along theelectrode elongate body 1059 of the electrode catheter 1057, where theconductive elements 1063 conduct electrical current to combinations ofone or more of the plurality of electrodes 1025. As illustrated, thefirst anchor 1029 is positioned between the inflatable balloon 1013 andthe plurality of electrodes 1025 positioned along the peripheral surfaceof the electrode elongate body 1059.

The catheter 1000 further includes an attachment ring 1065 joined to theelectrode catheter 1057 and positioned around the peripheral surface1061 of the elongate catheter body 1001 proximal to both the firstanchor 1029 and the inflatable balloon 1013. In one example, theattachment ring 1065 holds a distal end 1067 of the electrode catheter1057 in a static relationship to the elongate catheter body 1001. Fromthis position, a portion 1039 of the electrode elongate body 1059 thatincludes the plurality of electrodes 1025 can be made to curve in apredefined radial direction, as previously discussed. The configurationof the portion 1039 of the electrode elongate body 1059 that includesthe plurality of electrodes 1025 that curves can have any of theconfigurations and curvature mechanisms as discussed herein.

FIG. 10 also illustrates an elongate delivery sheath 1051 having a lumen1053 that extends over the peripheral surface of the elongate catheterbody 1001 and the electrode catheter 1057. The elongate delivery sheath1051, in a first position, can have the first anchor 1029 positionedwithin the lumen 1053 of the elongate delivery sheath 1051. As theelongate delivery sheath 1051 moves relative to the peripheral surface1007 of the elongate body 1001 and the peripheral surface 1061 of theelectrode catheter 1057, the first anchor 1029 extends from (e.g., awayfrom) the peripheral surface 1007 of the elongate body 1001.

Referring now to FIG. 11, a catheter system 1169 is shown in accordancewith an example of the disclosure. The catheter system 1169 includes anelongate catheter body 1102 having a first end 1104, a second end 1106,a peripheral surface 1176 and an interior surface 1184 defining aninflation lumen 1194 that extends at least partially between the firstend 1104 and the second end 1106 of the elongate catheter body 1102. Theelongate catheter body 1102 includes an elongate radial axis 1108defined by an intersection of a first plane 1110 and a second plane 1112perpendicular to the first plane 1110, where the elongate radial axis1108 extends through the first end 1104 and the second end 1106 of theelongate catheter body 1102.

The catheter system 1169 further includes an inflatable balloon 1178 onthe peripheral surface 1176 of the elongate catheter body 1102. Theinflatable balloon 1178 has a balloon wall 1188 with an interior surface1190 that, along with a portion of the peripheral surface 1176 of theelongate catheter body 1102, defines a fluid tight volume 1192. Theinflation lumen 1194 includes a first opening 1196 into the fluid tightvolume 1192 of the inflatable balloon 1178 and a second opening 1198proximal to the first opening 1196 to allow for a fluid to move in andout of the volume 1192 to inflate and deflate the balloon 1178.

The catheter system 1169 further includes an electrode cage 11690 havingtwo or more ribs 1171 that extend radially away from the peripheralsurface 1176 of the elongate catheter body 1102 towards the inflatableballoon 1178. As illustrated, each of the ribs 1171 of the electrodecage 11690 have a first end 11692 that extends away from the elongatecatheter body 1101 towards the inflatable balloon 1178. Each of thefirst ends 11692 of the ribs 1171 of the electrode cage 11690 is freerelative to every other first end of the ribs 1171. In addition, theribs 1171 of the electrode cage 1169 curve into a first half 1116 of thefirst plane 1110. Each of the ribs 1171 of the electrode cage 1169 alsoincludes one or more electrodes 1125. The one or more electrodes 1125 oneach of the ribs 1171 form an electrode array on the first half 1116 ofthe first plane 1110. The catheter system 1169 further includesconductive elements 1120 extending through and/or along the ribs 1171 ofthe electrode cage 1169 and the elongate catheter body 1101, where theconductive elements 1120 conduct electrical current to combinations ofone or more electrodes 1125 in the electrode array.

The catheter system 1169 also includes an anchoring cage 1173 having twoor more of the ribs 1171 that extend radially away from the peripheralsurface 1176 of the elongate catheter body 1101 towards the inflatableballoon 1178. As illustrated, the two or more ribs 1171 of the anchoringcage 1173 curve into the second half 1134 of the first plane 1110. Inthe illustrated example, the two or more ribs 1171 of the anchoring cage1173 do not include any electrodes. In some examples, one or more of theribs 1171 of the anchoring cage 1173 include one or more electrodes.

The catheter system 1169 can further include a second inflatable balloonon the peripheral surface 1176 of the elongate catheter body 1101. Forexample, the elongate catheter body 1101 can further include a third endand a second interior surface defining a second inflation lumen thatextends at least partially between the first end and the third end ofthe elongate catheter body 1101. The second inflatable balloon may belocated on the peripheral surface 1176 of the elongate catheter body1101 adjacent the third end of the elongate catheter body 1101. As withthe first inflatable balloon 1178, the second inflatable balloon mayinclude a balloon wall with an interior surface that, along with aportion of the peripheral surface 1176 of the elongate catheter body1101, defines a fluid tight volume. The second inflation lumen mayinclude a first opening into the fluid tight volume of the secondinflatable balloon and a second opening proximal to the first opening toallow for a fluid to move in and out of the volume to inflate anddeflate the second balloon.

FIG. 11 also illustrates the elongate delivery sheath 1151 having alumen 1153 that extends over the peripheral surface of the elongatecatheter body 1101 and the ribs 1171 of both the electrode cage 1169 andthe anchoring cage 1173. The elongate delivery sheath 1151, in a firstposition, can have the ribs 1171 of both the electrode cage 1169 and theanchoring cage 1173 within the lumen 1153 of the elongate deliverysheath 1151. As the elongate delivery sheath 1151 moves relative to theperipheral surface 1107 of the elongate body 1101, the ribs 1171 of theelectrode cage 1169 extend from the elongate body 1101 to curve into thefirst half 1116 of the first plane 1110 and the ribs 1171 of theanchoring cage 1173 extend from the elongate body 1101 to curve into thesecond half 1134 of the first plane 1110.

Referring now to FIG. 12A, there is shown a perspective view of anexample of a catheter 1200. The catheter 1200 includes an elongate body1202 having a first end 1204 and a second end 1206 distal from the firstend 1204. As illustrated, the elongate body 1202 includes a longitudinalcenter axis 1208 extending between the first end 1204 and the second end1206 of the elongate body 1202. The elongate body 1202 also includes aportion 1210 that has three or more surfaces 1212 defining a convexpolygonal cross-sectional shape taken perpendicularly to thelongitudinal center axis 1208.

As used herein, the convex polygonal cross-sectional shape of theelongate body 1202 includes those shapes for which every internal angleis less than 180 degrees and where every line segment between twovertices of the shape remains inside or on the boundary of the shape.Examples of such shapes include, but are not limited to, triangular,rectangular (as illustrated in FIG. 12A), square, pentagon and hexagon,among others.

As illustrated, the catheter 1200 includes one or more (e.g., two ormore), electrodes 1214 on one surface of the three or more surfaces 1212of the elongate body 1202. Conductive elements 1216 extend throughand/or along the elongate body 1202, where the conductive elements 1216can be used, for example as discussed herein, to conduct electricalcurrent to combinations of the one or more electrodes 1214. Each of theone or more electrodes 1214 is coupled to a corresponding conductiveelement 1216. In some examples, the conductive elements 1216 areelectrically isolated from each other and extend through and/or alongthe elongate body 1202 from each respective electrode 1214 through thefirst end 1204 of the elongate body 1202. The conductive elements 1216may terminate at a connector port, where each of the conductive elements1216 can be releasably coupled to a stimulation system, such as thestimulation systems described herein. In some examples, the conductiveelements 1216 are permanently coupled to the stimulation system (e.g.,not releasably coupled). The stimulation system can be used to providestimulation electrical energy that is conducted through the conductiveelements 1216 and delivered across combinations of the one or moreelectrodes 1214. The one or more electrodes 1214 may be electricallyisolated from one another and the elongate body 1202 may be formed of anelectrically insulating material as discussed herein. As illustrated,the one or more electrodes 1214 are located only on the one surface ofthe three or more surfaces 1212 of the elongate body 1202, in accordancewith one example.

There can be a variety of the number and the configuration of the one ormore electrodes 1214 on the one surface of the three or more surfaces1212 of the elongate body 1202. For example, as illustrated, the one ormore electrodes 1214 can be configured as an array of electrodes, wherethe number of electrodes and their relative position to each other canvary depending upon the desired implant (e.g., deployment or target)location. As discussed herein, the one or more electrodes 1214 can beconfigured to allow for electrical current to be delivered from and/orbetween different combinations of the one or more electrodes 1214. So,for example, the electrodes in the array of electrodes can have arepeating pattern where the electrodes are equally spaced from eachother. For example, the electrodes in the array of electrodes can have acolumn and row configuration (as illustrated in FIG. 12A).Alternatively, the electrodes in the array of electrodes can have aconcentric radial pattern, where the electrodes are positioned so as toform concentric rings of the electrodes. Other patterns are possible,where such patterns can either be repeating patterns or random patterns.

As illustrated, the one or more electrodes 1214 have an exposed face1218. The exposed face 1218 of the electrode 1214 provides theopportunity for the electrode 1214, when implanted (temporarily or foran extended duration of time) in the patient, to be placed intoproximity and/or in contact with vascular tissue of the patient (e.g.,of the right or left pulmonary artery), as opposed to facing into thevolume of blood in the artery or other vessel, lumen or organ. As theone or more electrodes 1214 are located on one surface of the three ormore surfaces 1212 of the elongate body 1202, the electrodes 1214 can beplaced into direct proximity to and/or in contact with the tissue of anycombination of the main pulmonary artery, the left pulmonary arteryand/or the right pulmonary artery.

By locating the one or more electrodes 1214 on the one surface of thethree or more surfaces 1212, the exposed face 1218 of the electrode canbe positioned inside the patient's vasculature to face and/or contactthe tissue of the main pulmonary artery, the left pulmonary arteryand/or the right pulmonary artery. When the one or more electrodes 1214are in contact with luminal surface of the patient's vasculature, theone or more electrodes 1214 will be pointing away from the majority ofthe blood volume of that region of the pulmonary artery, therebyallowing the electrical pulses from the one or more electrodes 1214 tobe directed into the tissue adjacent the implant location, instead ofbeing directed into the blood volume.

The exposed face 1218 of the one or more electrodes 1214 can have avariety of shapes. For example, the exposed face 1218 can have a flatplanar shape. In this example, the exposed face 1218 of the electrodes1214 can be co-planar with the one surface of the three or more surfaces1212 of the elongate body 1202. In an alternative example, the exposedface 1218 of the electrodes 1214 can have a semi-hemispherical shape.Other shapes for the exposed face 1218 of the electrodes 1214 caninclude semi-cylindrical, wave-shaped, and zig-zag-shaped. The exposedface 1218 of the electrodes 1214 can also include one or more anchorstructures. Examples of such anchor structures include hooks that canoptionally include a barb. Similarly, the electrodes 1214 can be shapedto also act as anchor structures.

In one example, the one surface of the three or more surfaces 1112 ofthe elongate body 1102 that includes the exposed face 1218 of the one ormore electrodes 1214 can further include anchor structures 1220 thatextend above the one surface of the three or more surfaces 1212. Asillustrated, the anchor structures 1220 can include portions that cancontact the vascular tissue in such a way that the movement of the oneor more electrodes 1214 at the location where they contact the vasculartissue is reduced (e.g., minimized). The anchor structures 1220 can havea variety of shapes that may help to achieve this goal. For example, theanchor structures 1220 can have a conical shape, where the vertex of theconical shape can contact the vascular tissue. In one example, theanchor structures 1220 have a hook configuration (with or without abarb). In an additional example, one or more of the anchor structures1220 can be configured as an electrode.

As illustrated, the elongate body 1202 of the catheter 1200 can alsoinclude a portion 1222 with a circular cross-section shape takenperpendicularly to the longitudinal center axis 1208. The elongate body1202 of catheter 1200 also includes a surface 1224 defining a guide-wirelumen 1226 that extends through the elongate body 1202. The guide-wirelumen 1226 may have a diameter that is sufficiently large to allow theguide wire to freely pass through the guide-wire lumen 1226. Theguide-wire lumen 1226 can be positioned concentrically relative to thelongitudinal center axis 1208 of the elongate body 1202.

Alternatively, and as illustrated in FIG. 12A, the guide-wire lumen 126can be positioned eccentrically relative to the longitudinal center axis1208 of the elongate body 1202. When the guide-wire lumen 1226 ispositioned eccentrically relative to the longitudinal center axis 1208,the guide-wire lumen 1226 has a wall thickness 1228 takenperpendicularly to the longitudinal center axis that is greater than awall thickness 1230 of a remainder of the catheter taken perpendicularlyto the longitudinal center axis. For this configuration, the differencesin wall thickness 1228 and 1230 help to provide the elongate body 1202with a preferential direction in which to bend. For example, the wallthickness 1228 of the elongate body 1202 being greater than the wallthickness 1230 causes the side of the elongate body 1102 with thegreater wall thickness to preferentially have the larger radius ofcurvature when the elongate body 1102 bends, in accordance with severalexamples. By positioning the exposed face 1218 of the one or moreelectrodes 1214 on the side of the elongate body 1202 having the greaterwall thickness (e.g., wall thickness 1228), the one or more electrodes1214 can be more easily and predictably brought into contact with theluminal surface of the vasculature in and around the main pulmonaryartery and at least one of the right and left pulmonary arteries.

The catheter 1200 shown in FIG. 12A can be positioned in the mainpulmonary artery and/or one or both of the left and right pulmonaryarteries of the patient, such as described herein. To accomplish this, apulmonary artery guide catheter is introduced into the vasculaturethrough a percutaneous incision and guided to the right ventricle usingknown techniques. For example, the pulmonary artery guide catheter canbe inserted into the vasculature via a peripheral vein of the arm (e.g.,as with a peripherally inserted central catheter), via a peripheral veinof the neck or chest (e.g., as with a Swan-Ganz catheter approach), or aperipheral vein of the leg (e.g., a femoral vein). Other approaches caninclude, but are not limited to, an internal jugular approach. Changesin a patient's electrocardiography and/or pressure signals from thevasculature can be used to guide and locate the pulmonary artery guidecatheter within the patient's heart. Once in the proper location, aguide wire can be introduced into the patient via the pulmonary arteryguide catheter, where the guide wire is advanced into the main pulmonaryartery and/or one of the pulmonary arteries (e.g., left and rightpulmonary arteries). Using the guide-wire lumen 1226, the catheter 1200can be advanced over the guide wire so as to position the catheter 1200in the main pulmonary artery and/or one or both of the left and rightpulmonary arteries of the patient, for example as described herein.Various imaging modalities can be used in positioning the guide wire ofthe present disclosure in the main pulmonary artery and/or one of theleft and right pulmonary arteries of the patient. Such imagingmodalities include, but are not limited to, fluoroscopy, ultrasound,electromagnetic, and electropotential modalities.

Using a stimulation system, such as the stimulation systems discussedherein, stimulation electrical energy (e.g., electrical current orpulses) can be delivered across combinations of one or more of theelectrodes 1214. In accordance with several examples described herein,it is possible for the patient's cardiac response to the stimulationelectrical energy to be monitored and recorded for comparison to othersubsequent tests. It is appreciated that for any of the cathetersdiscussed herein any combination of electrodes, including referenceelectrodes (as discussed herein) positioned within or on the patient'sbody, can be used in providing stimulation to and sensing cardiacsignals from the subject (e.g., patient).

FIG. 12B illustrates another example of the catheter 1200. The catheter1200 includes the features and components as discussed above, adiscussion of which is not repeated but the element numbers are includedin FIG. 12B with the understanding that the discussion of these elementsis implicit. In addition, the elongate body 1202 of the catheter 1200includes a serpentine portion 1232 proximal to the one or moreelectrodes 1214. When implanted (e.g., deployed) in the vasculature ofthe patient, the serpentine portion 1232 of the elongate body 1202 canact as a “spring” to absorb and isolate the movement of the one or moreelectrodes 1214 from the remainder of the elongate body 1202 of thecatheter 1200. Besides having a serpentine shape, the serpentine portion1232 can have a coil like configuration. Other shapes that achieve theobjective of absorbing and isolating the movement of the one or moreelectrodes 1214 from the remainder of the elongate body 1202 of thecatheter 1200 once implanted may also be used as desired and/orrequired. During delivery of the catheter 1200, the presence of theguide wire in the guide-wire lumen 1226 can help to temporarilystraighten the serpentine portion 1232 of the elongate body 1202.

Referring now to FIG. 12C, there is shown an additional example of thecatheter 1200 as provided herein. The catheter 1200 can include thefeatures and components as discussed above for the catheters describedin connection with FIGS. 12A and 12B, a discussion of which is notrepeated but the element numbers are included in FIG. 12C with theunderstanding that the discussion of these elements is implicit. Inaddition, the catheter 1200 of the present example includes aninflatable balloon 1234. As illustrated, the elongate body 1202 includesa peripheral surface 1236, where the inflatable balloon 1234 is locatedon the peripheral surface 1236 of the elongate body 1202. The inflatableballoon 1234 includes a balloon wall 1238 with an interior surface 1240that, along with a portion 1242 of the peripheral surface 1236 of theelongate body 1202, defines a fluid tight volume 1244.

The elongate body 1202 further includes a surface 1245 that defines aninflation lumen 1246 that extends through the elongate body 1202. Theinflation lumen 1246 includes a first opening 1248 into the fluid tightvolume 1244 of the inflatable balloon 1234 and a second opening 1250proximal to the first opening 1248 to allow for a fluid to move in andout of the fluid tight volume 1244 to inflate and deflate the balloon1234. A syringe, or other known devices, containing the fluid (e.g.,saline or a gas (e.g., oxygen)) can be used to inflate and deflate theballoon 334.

The catheter 1200 shown in FIG. 12C can be positioned in the mainpulmonary artery and/or one or both of the right and left pulmonaryarteries of the patient, for example as described herein. As discussedherein, a pulmonary artery guide catheter is introduced into thevasculature through a percutaneous incision, and guided to the rightventricle. Once in the proper location, the balloon 1234 can beinflated, as described, to allow the catheter 1200 to be carried by theflow of blood from the right ventricle to the main pulmonary arteryand/or one of the pulmonary arteries. Additionally, various imagingmodalities can be used in positioning the catheter of the presentdisclosure in the main pulmonary artery and/or one of the pulmonaryarteries of the patient. Such imaging modalities include, but are notlimited to, fluoroscopy, ultrasound, electromagnetic, andelectropotential modalities.

The catheter 1200 can be advanced along the main pulmonary artery untilthe second end 1206 of the catheter 1200 contacts the top of the mainpulmonary artery (e.g., a location distal to the pulmonary valve andadjacent to both the pulmonary arteries). Once the second end 1206 ofthe catheter 1200 reaches the top of the main pulmonary artery thepulmonary artery guide catheter can be moved relative to the catheter1200 so as to deploy the catheter 1200 from the pulmonary artery guidecatheter.

Markings can be present on the peripheral surface of the catheter body1202, where the markings start and extend from the first end 1202towards the second end 1206 of the catheter body 1202. The distancebetween the markings can be of units (e.g., millimeters, inches, etc.),which can allow the length between the second end 1206 of the catheter1200 and the top of the main pulmonary artery to be determined.

The ability to measure this distance from the top of the main pulmonaryartery may be helpful in placing the one or more electrodes 1214 in adesired location (e.g., at a location within the main pulmonary artery).In addition to measuring the distance from which the second end 1206 ofthe elongate body 1202 is placed from the top of the main pulmonaryartery, the elongate body 1202 can also be used to identify, or map, anoptimal position for the one or more electrodes 1214 within thevasculature. For example, the second end 1206 of the elongate body 1202can be positioned at the desired distance from the top of the mainpulmonary artery using the markings on the peripheral surface of thecatheter body 1202.

Using the stimulation system, such as the stimulations systems discussedherein, stimulation electrical energy (e.g., electrical current orelectrical pulses) can be delivered across combinations of the one ormore electrodes 1214. It is possible for the patient's cardiac responseto the stimulation electrical energy to be monitored and recorded forcomparison to other subsequent tests. It is appreciated that for any ofthe catheters discussed herein any combination of electrodes, includingreference electrodes (as discussed herein) positioned within or on thepatient's body, can be used in providing stimulation to and sensingcardiac signals from the patient.

Referring now to FIG. 12D, there is shown an additional example of thecatheter 1200. The catheter 1200 can include the features and componentsas the catheters discussed above in connection with FIGS. 12A-12C, adiscussion of which is not repeated but the element numbers are includedin FIG. 12D with the understanding that the discussion of these elementsis implicit. In addition, the catheter 1200 of the present exampleincludes a surface 1252 defining a deflection lumen 1254. The deflectionlumen 1254 includes a first opening 1256 and a second opening 1258 inthe elongate body 1202. In one example, the second opening 1258 isopposite the one or more electrodes 1214 on one surface of the three ormore surfaces 1212 of the elongate body 1202.

The catheter 1200 further includes an elongate deflection member 1260.The elongate deflection member 1260 includes an elongate body 1261having a first end 1263 and a second end 1265. The elongate deflectionmember 1260 extends through the first opening 1256 to the second opening1258 of the deflection lumen 1254. The deflection lumen 1254 has a size(e.g., a diameter) sufficient to allow the deflection member 1260 topass through the deflection lumen 1254 with the first end 1263 of thedeflection member 1260 proximal to the first end 1204 of the elongatebody 1202 and the second end 1265 of the deflection member 1260extendable from the second opening 1258 of the deflection lumen 1254.Pressure applied from the first end 1263 of the deflection member 1260can cause the deflection member 1260 to move within the deflection lumen1254. For example, when pressure is applied to the deflection member1260 to move the first end 1263 of the deflection member 1260 towardsthe first opening 1256 of the deflection lumen 1254, the pressure causesthe second end 1265 of the deflection member 1260 to extend from thesecond opening 1258.

As generally illustrated, the elongate deflection member 1260 can beadvanced through the deflection lumen 1254 so that elongate deflectionmember 1260 extends laterally away from the one or more electrodes 1214on the one surface of the three or more surfaces 1212 of the elongatebody 1202. The elongate deflection member 1260 can be of a length andshape that allows the elongate deflection member 1260 to be extended adistance sufficient to bring the one or more electrodes 1214 intocontact with the vascular luminal surface (e.g., a posterior surface ofthe main pulmonary artery and/or one or both of the pulmonary arteries)with a variety of pressures. Optionally, the elongate deflection member1260 can be configured to include one or more of the electrodes 1214,such as discussed herein.

For the various examples, the elongate body 1261 of the deflectionmember 1260 is formed of a flexible polymeric material. Examples of suchflexible polymeric material include, but are not limited to, medicalgrade polyurethanes, such as polyester-based polyurethanes,polyether-based polyurethanes, and polycarbonate-based polyurethanes;polyamides, polyamide block copolymers, polyolefins such as polyethylene(e.g., high density polyethylene); and polyimides, among others.

In one example, the elongate body 1261 of the elongate deflection member1260 also includes one or more support wires. The support wires can beencased in the flexible polymeric material of the elongate body 1261,where the support wires can help to provide both column strength and apredefined shape to the elongate deflection member 1260. For example,the support wires can have a coil shape that extends longitudinallyalong the length of the elongate body 1261. In accordance with severalexamples, the coil shape advantageously allows for the longitudinalforce applied near or at the first end 1263 of the deflection member1260 to be transferred through the elongate body 1261 so as to laterallyextend the second end 1265 of the deflection member 1260 from the secondopening 1258 of the deflection lumen 1254.

The support wires can also provide the deflection member 1260 with apredetermined shape upon laterally extending from the second opening1258 of the deflection lumen 1254. The predetermined shape can bedetermined to engage the luminal wall of the pulmonary artery in orderto bring the electrodes 1214 into contact with the vascular tissue. Thepredetermined shape and the support wires can also help to impartstiffness to the deflection member 1260 that is sufficient to maintainthe electrodes 1214 on the luminal wall of the pulmonary artery underthe conditions within the vasculature of the subject (e.g., patient).The support wires can be formed of a variety of metals or metal alloys.Examples of such metals or metal alloys include surgical grade stainlesssteel, such as austenitic 316 stainless among others, and the nickel andtitanium alloy known as Nitinol. Other metals and/or metal alloys can beused as desired and/or required.

The catheter 1200 shown in FIG. 12D can be positioned in the mainpulmonary artery and/or one or both of the left and right pulmonaryarteries of the patient, such as described herein. In accordance withseveral methods, a pulmonary artery guide catheter is introduced intothe vasculature through a percutaneous incision, and guided to the rightventricle (e.g., using a Swan-Ganz catheterization approach). Once inthe proper location, the balloon 1234 can be inflated, as described, toallow the catheter 1200 to be carried by the flow of blood from theright ventricle to the main pulmonary artery and/or one of the right andleft pulmonary arteries. Additionally, various imaging modalities can beused in positioning the catheter in the main pulmonary artery and/or oneof the right and left pulmonary arteries of the patient. Such imagingmodalities include, but are not limited to, fluoroscopy, ultrasound,electromagnetic, and electropotential modalities.

The catheter 1200 can be advanced along the main pulmonary artery untilthe second end 1206 of the catheter 1200 contacts the top of the mainpulmonary artery (e.g., a location distal to the pulmonary valve andadjacent to both the pulmonary arteries). Once the second end 1206 ofthe catheter 1200 reaches the top of the main pulmonary artery thepulmonary artery guide catheter can be moved relative to the catheter1200 so as to deploy the catheter 1200 from the pulmonary artery guidecatheter.

Markings, as discussed herein, can be present on the peripheral surfaceof the catheter body 1202 that can assist in positioning the catheter1200 within the main pulmonary artery. The ability to measure thisdistance from the top of the main pulmonary artery may be helpful inplacing the one or more electrodes 1214 in a desired location (e.g., alocation within the main pulmonary artery). In addition to measuring thedistance from which the second end 1206 of the elongate body 1202 isplaced from the top of the main pulmonary artery, the elongate body 1202can also be used to identify, or map, an optimal position for the one ormore electrodes 1214 within the vasculature. For example, the second end1206 of the elongate body 1202 can be positioned at the desired distancefrom the top of the main pulmonary artery using the markings on theperipheral surface of the catheter body 1202.

When desired, the elongate deflection member 1260 can be extendedlaterally from the elongate body 1202 to a distance sufficient to causethe one surface of the three or more surfaces 1212 of the elongate body1202 having the one or more electrodes to contact a surface of the mainpulmonary artery, such as the anterior surface of the main pulmonaryartery, and thereby bring the one or more electrodes 1214 into contactwith the main pulmonary artery or one of the pulmonary arteries (theleft pulmonary artery or the right pulmonary artery). The elongatedeflection member 1260, as will be appreciated, biases and helps toplace the one or more electrodes 1214 along the vessel surface (e.g.,along the posterior surface of the main pulmonary artery or one of thepulmonary arteries (the left pulmonary artery or the right pulmonaryartery)).

Due to its adjustable nature (e.g., how much pressure is applied to theelongate deflection member 1260), the elongate deflection member 1260can be used to bring the one or more electrodes 1214 into contact withthe luminal surface of the main pulmonary artery or one of the pulmonaryarteries with a variety of pressures. So, for example, the elongatedeflection member 1260 can bring the one or more electrodes 1214 intocontact with the luminal surface of the main pulmonary artery or one ofthe left and right pulmonary arteries with a first pressure. Using thestimulation system, such as the stimulation systems discussed herein,stimulation electrical energy (e.g., electrical current or electricalpulses) can be delivered across combinations of the one or moreelectrodes 1214 in the electrode array. It is possible for the patient'scardiac response to the stimulation electrical energy to be monitoredand recorded for comparison to other subsequent tests.

It is appreciated that for any of the catheters discussed herein anycombination of electrodes, including reference electrodes (as discussedherein) positioned within or on the patient's body, can be used inproviding stimulation to and sensing cardiac signals from the patient.

If necessary, the distance the elongate deflection member 1260 extendslaterally from the elongate body 1202 can be changed (e.g., madeshorter) to allow the elongate body 1202 to be rotated in either aclockwise or counter-clockwise direction, thereby repositioning the oneor more electrodes 1214 in contact with the luminal surface of the mainpulmonary artery or one of the pulmonary arteries. The stimulationsystem can again be used to deliver stimulation electrical energy acrosscombinations of one or more of the electrodes 1214 in the electrodearray. The patient's cardiac response to this subsequent test can thenbe monitored and recorded for comparison to previous and subsequenttest. In this way, a preferred location for the position of the one ormore electrodes 1214 along the luminal surface of the main pulmonaryartery or one of the left and right pulmonary arteries can beidentified. Once identified, the elongate deflection member 1260 can beused to increase the lateral pressure applied to the one or moreelectrodes, thereby helping to better anchor the catheter 1200 in thepatient.

FIG. 13 provides a perspective view of a catheter 1330 positioned in theheart 200 of the subject (e.g., patient), where one or more of theelectrodes 1344 is contacting the posterior surface 221 and/or superiorsurface 223 of, for example, the right pulmonary artery 206. FIG. 13also illustrates the one or more of the electrodes 1344 contacting theposterior surface 221 and/or superior surface 223 of the right pulmonaryartery 208 at a position that is superior to the branch point 207. FIG.13 further illustrates that at least a portion of the catheter 1330 ispositioned in contact with a portion of the surface defining the branchpoint 207.

As illustrated, the pulmonary trunk has a diameter 1356 taken across aplane 1358 perpendicular to both the left lateral plane 220 and theright lateral plane 216. In one example, the electrode array of thecatheter 1330 is positioned in an area 1360 that extends distally nomore than three times the diameter of the pulmonary trunk 202 to theright of the branch point 207. This area 1360 is shown withcross-hatching in FIG. 13.

The right pulmonary artery 206 can also include a branch point 1362 thatdivides the right pulmonary artery 206 into at least two additionalarteries 1364 that are distal to the branch point 207 defining the leftpulmonary artery 208 and the right pulmonary artery 206. As illustrated,the electrode array can be positioned between the branch point 207defining the left pulmonary artery 208 and the right pulmonary artery206 and the branch point 1362 that divides the right pulmonary artery206 into at least two additional arteries 1364.

Once in position, electrical current can be provided from or to one ormore of the electrodes 1344. Using a first sensor 1352 a value of anon-cardiac parameter of the patient can be measured in response to theelectrical current from or to one or more of the electrodes 1344. Fromthe value of the non-cardiac parameter, changes can be made to which ofthe one or more electrodes are used to provide the electrical current inresponse to the value of the cardiac parameter. Changes can also be madeto the nature of the electrical current provided in response to thevalue of the non-cardiac parameter. Such changes include, but are notlimited to, changes in voltage, amperage, waveform, frequency and pulsewidth by way of example. It is possible to change combinations ofelectrodes used and the nature of the electrical current provided by theelectrodes. In addition, the electrodes of the one or more electrodes onthe posterior surface of the right pulmonary artery 206 can be moved inresponse to one or more of the values of the non-cardiac parameter.Examples of such a cardiac parameter include, but are not limited to,measuring a pressure parameter, an acoustic parameter, an accelerationparameter and/or an electrical parameter (e.g., ECG) of the heart of thepatient as the cardiac parameter. An example of such a pressureparameter can include, but is not limited to, measuring a maximumsystolic pressure of the heart of the patient as the pressure parameter.Other suitable cardiac parameters are discussed herein.

Moving the electrodes of the one or more electrodes on the posteriorand/or superior surface of the right pulmonary artery 206 in response toone or more of the values of the cardiac parameter can be done byphysically moving the one or more electrodes of the catheter 1330 to adifferent position on the posterior and/or superior surface of the rightpulmonary artery 206, electronically moving which electrodes of the oneor more electrodes are being used to provide the electrical current fromor to the electrode array (while not physically moving the one or moreelectrodes of the catheter 1330) or a combination of these two actions.

As discussed herein, neuromodulation according to the present disclosurecan be accomplished by applying electrical current to the rightpulmonary artery 206. Preferably, neuromodulation of the presentdisclosure includes applying the electrical current to the posteriorand/or superior wall of the right pulmonary artery 206. The electricalcurrent is thereby applied to the autonomic cardiopulmonary nervessurrounding the right pulmonary artery 206. These autonomiccardiopulmonary nerves can include the right autonomic cardiopulmonarynerves and the left autonomic cardiopulmonary nerves. The rightautonomic cardiopulmonary nerves include the right dorsal medialcardiopulmonary nerve and the right dorsal lateral cardiopulmonarynerve. The left autonomic cardiopulmonary nerves include the leftventral cardiopulmonary nerve, the left dorsal medial cardiopulmonarynerve, the left dorsal lateral cardiopulmonary nerve, and the leftstellate cardiopulmonary nerve.

As illustrated and discussed in reference to FIG. 13, the one or moreelectrodes of the catheter are contacting the posterior surface of theright pulmonary artery 206. From this location, the electrical currentdelivered through the one or more electrodes may be better able to treatand/or provide therapy (including adjuvant therapy) to the patientexperiencing a variety of cardiovascular medical conditions, such asacute heart failure. The electrical current can elicit responses fromthe autonomic nervous system that may help to modulate a patient'scardiac contractility. The electrical current is intended to affectheart contractility more than the heart rate, thereby helping toimproving hemodynamic control while possibly minimizing unwantedsystemic effects.

Referring now to FIG. 14A, there is shown an additional example of acatheter 1462. The catheter 1462 includes an elongate body 1402 having aperipheral surface 1436 and a longitudinal center axis 1408 extendingbetween a first end 1404 and a second end 1406. The catheter 1462 caninclude the features and components as discussed above for catheters100, 200, 300 and/or 400, a discussion of which is not repeated but theelement numbers are included in FIG. 14A with the understanding that thediscussion of these elements is implicit.

The catheter 1462 of the present example includes an inflatable balloon1434. As illustrated, the elongate body 1402 includes a peripheralsurface 1436, where the inflatable balloon 1434 is located on theperipheral surface 1436 of the elongate body 1402. The inflatableballoon 1434 includes a balloon wall 1438 with an interior surface 1440that along with a portion 1442 of the peripheral surface 1436 of theelongate body 1402 defines a fluid tight volume 1444.

The elongate body 1402 further includes a surface 1445 that defines aninflation lumen 1446 that extends through the elongate body 1402. Theinflation lumen 1446 includes a first opening 1448 into the fluid tightvolume 1444 of the inflatable balloon 1434 and a second opening 1450proximal to the first opening 1448 to allow for a fluid to move in thefluid tight volume 1444 to inflate and deflate the balloon 1434. Asyringe, or other known devices, containing the fluid (e.g., saline or agas (e.g., oxygen)) can be used to inflate and deflate the balloon 1434.

The elongate body 1402 further includes an offset region 1464 defined bya series of predefined curves along the longitudinal center axis 1408.As used herein, “predefined curves” are curves formed in the elongatebody 1402 during the production of the catheter 1462, where whendeformed such curves provide a spring like force to return to theirpre-deformation shape (e.g., their original shape). As illustrated, theseries of predefined curves includes a first portion 1466 that has afirst curve 1468 in the longitudinal center axis 1408 followed by asecond curve 1470 in the longitudinal center axis 1408 of the elongatebody 1402. The length and degree of each of the first curve 1468 andsecond curve 1470, along with the distance between such curves, helps todefine the height of the offset region 1464. As discussed herein, theheight of the offset region 1464 can be determined by the inner diameterof one or more locations along the main pulmonary artery and/or one ofthe right and left pulmonary arteries.

The first portion 1466 of the elongate body 1402 is followed by a secondportion 1472 of the elongate body 1402. The longitudinal center axis1408 along the second portion 1472 can have a zero curvature (e.g., astraight line), as illustrated in FIG. 14A. The second portion 1472 ofthe elongate body 1402 is followed by a third portion 1474 of theelongate body 1402. The longitudinal center axis 1408 transitions fromthe second portion 1472 along a third curve 1476, which then transitionsinto a fourth curve 1478. As illustrated, after the fourth curve 1478,the longitudinal center axis 1408 is approximately co-linear with thelongitudinal center axis 1408 leading up to the first curve 1468. It isnoted that the curves of the first portion 1466 and the second portion1474 can also all be in approximately the same plane. It is, however,possible that the curves of the first portion 1466 and the secondportion 1474 are not in the same plane. For example, when the curves ofthe first portion 1466 and the second portion 1474 are not in the sameplane the longitudinal center axis 1408 can include a helical curvethrough these portions of the elongate body 1402. Other shapes are alsopossible.

The elongate body 1402 can further include one or more electrodes 1414,for example as discussed herein, along the second portion 1472 of theoffset region 1464 of the elongate body 1402. As illustrated, the one ormore electrodes 1414 can be on the surface of the elongate body 1402 inthe second portion 1472 of the offset region 1464. Conductive elements1416 extend through and/or along the elongate body 1402, where theconductive elements 1416 can be used, as discussed herein, to conductelectrical current to combinations of the one or more electrodes 1414.Each of the one or more electrodes 1414 is coupled to a correspondingconductive element 1416. The conductive elements 1416 are electricallyisolated from each other and extend through and/or along the elongatebody 1402 from each respective electrode 1414 through the first end 1404of the elongate body 1402. The conductive elements 1416 terminate at aconnector port, where each of the conductive elements 1416 can bereleasably coupled to a stimulation system, for example as discussedherein. It is also possible that the conductive elements 1416 arepermanently coupled to the stimulation system (e.g., not releasablycoupled). The stimulation system can be used to provide stimulationelectrical energy (e.g., electrical current or electrical pulses) thatis conducted through the conductive elements 1416 and delivered acrosscombinations of the one or more electrodes 1414. In some examples, theone or more electrodes 1414 are electrically isolated from one another,where the elongate body 1402 is formed of an electrically insulatingmaterial.

There can be wide variety for the number and configuration of the one ormore electrodes 1414 on the one surface of the second portion 1472 ofthe elongate body 1402. For example, as illustrated, the one or moreelectrodes 1414 can be configured as an array of electrodes, where thenumber of electrodes and their relative position to each other can varydepending upon the desired implant location. As discussed herein, theone or more electrodes 1414 can be configured to allow for electricalcurrent to be delivered from and/or between different combinations ofthe one or more electrodes 1414. The electrodes in the array ofelectrodes can have a repeating pattern where the electrodes are equallyspaced from each other. So, for example, the electrodes in the array ofelectrodes can have a column and row configuration. Alternatively, theelectrodes in the array of electrodes can have a concentric radialpattern, where the electrodes are positioned so as to form concentricrings of the electrodes. Other patterns are possible, where suchpatterns can either be repeating patterns or random patterns. Asdiscussed herein, the catheter 1462 further includes conductive elements1416 extending through and/or along the elongate body, where theconductive elements 1416 conduct electrical current to combinations ofthe one or more electrodes 1414.

As discussed herein, the length and degree of each of the curves, alongwith the distance between such curves helping to define the firstportion 1466 and the third portion 1474 of the longitudinal center axis1408, helps to define the relative height of the offset region 1464. Forthe various examples, the height of the offset region 1464 can bedetermined by the inner diameter of one or more locations along the mainpulmonary artery and/or one of the right and left pulmonary arteries. Inthis way, the first portion 1466 and the third portion 1474 can bringthe second portion 1472 and the one or more electrodes 1414 on thesurface of the elongate body 1402 into contact with the vascular wall ofthe patient in the main pulmonary artery and/or one of the left or rightpulmonary arteries. In other words, the transitions of the first portion1466 and the third portion 1474 of the elongate body 1402 in the offsetregion 1464 can act to bias the second portion 1472 and the one or moreelectrodes 1414 against the vascular wall of the patient in the mainpulmonary artery and/or one of the right or left pulmonary arteries.

The elongate body 1402 further includes a surface 1424 defining aguide-wire lumen 1426 that extends through and/or along the elongatebody 1402. As provided herein, the guide-wire lumen 1426 can beconcentric relative to the longitudinal center axis 1408 of the elongatebody 1402 (as illustrated in FIG. 14A). Alternatively, the guide-wirelumen 1426 can be eccentric relative to the longitudinal center axis1408 of the elongate body 1402. As discussed herein, the guide-wirelumen 1426 can have a wall thickness 1428 that is greater than a wallthickness 1430 of a remainder of the catheter 1462 taken perpendicularlyto the longitudinal center axis 1408. In an additional example, aportion of the elongate body 1402 includes a serpentine portion, asdiscussed and illustrated herein, proximal to the one or more electrodes1414.

For the present example, a guide-wire used with the catheter 1462 canserve to temporarily “straighten” the offset region 1464 when theguide-wire is present in the guide-wire lumen 1426 that passes along theoffset region 1464. Alternatively, the guide-wire can be used to impartthe shape of the offset region 1464 to the catheter 1462. In thisexample, the elongate body 1402 of the catheter 1462 can have a straightshape (e.g., no predefined lateral shape). To impart the offset region1464 the guide wire is “shaped” (e.g., bent) to the desiredconfiguration of the offset region at point that corresponds to thedesired longitudinal location for the offset region on the elongate body1402. The offset region 1464 of the catheter 1462 can be provided byinserting the guide wire with the predefined lateral shape.

In FIG. 14A, the catheter 1462 of the present example further includes asurface 1452 defining a deflection lumen 1454, as discussed herein. Thecatheter 1462 further includes an elongate deflection member 1460, alsoas discussed herein. As generally illustrated, the elongate deflectionmember 1460 can be advanced through the deflection lumen 1454 so thatelongate deflection member 1460 extends laterally away from the one ormore electrodes 1414 on the second portion 1472 of the elongate body1402. The elongate deflection member 1460 can be of a length and shapethat allows the elongate deflection member 1460 to be extended adistance sufficient to bring the one or more electrodes 1414 intocontact with the vascular luminal surface (e.g., a posterior surface ofthe main pulmonary artery and/or one or both of the pulmonary arteries)with a variety of pressures.

In one example, the elongate body 1461 of the elongate deflection member1460 can also include one or more support wires 1481. The support wires1481 can be encased in the flexible polymeric material of the elongatebody 1461, where the support wires 1481 can help to provide both columnstrength and a predefined shape to the elongate deflection member 1460.For example, the support wires 1481 can have a coil shape that extendslongitudinally along the length of the elongate body 1461. In accordancewith several examples, the coil shape advantageously allows for thelongitudinal force applied near or at the first end 1463 of thedeflection member 1460 to be transferred through the elongate body 1461so as to laterally extend the second end 1465 of the deflection member1460 from the second opening 1458 of the deflection lumen 1454.

The support wires 1481 can also provide the deflection member 1460 witha predetermined shape upon laterally extending from the second opening1458 of the deflection lumen 1454. The predetermined shape can bedetermined to engage the luminal wall of the pulmonary artery in orderto bring the electrodes 1414 on the second portion 1472 of the offsetregion 1464 into contact with the vascular tissue. The predeterminedshape and the support wires 1481 can also help to impart stiffness tothe deflection member 1460 that is sufficient to maintain the electrodes1414 on the luminal wall of the pulmonary artery under the conditionswithin the vasculature of the patient.

The support wires 1481 can be formed of a variety of metals or metalalloys. Examples of such metals or metal alloys include surgical gradestainless steel, such as austenitic 316 stainless among others, and thenickel and titanium alloy known as Nitinol. Other metals and/or metalalloys can be used as desired and/or required.

Referring now to FIG. 14B, there is shown an additional example of acatheter 1462. The catheter 1462 can include the features and componentsof the catheters described above in connection with FIGS. 12A-12D and/or14A, a discussion of which is not repeated but the element numbers areincluded in FIG. 14B with the understanding that the discussion of theseelements is implicit.

The catheter 1462 seen in FIG. 14B is similar to the catheter 1462 ofFIG. 14A, where the elongate body 1402 of catheter 1462 further includesthree or more surfaces 1412 defining a convex polygonal cross-sectionalshape taken perpendicularly to the longitudinal center axis 1408, asdiscussed for the catheters 1200 herein. As illustrated, the one or moreelectrodes 1414 are on one surface of the three or more surfaces 1412 ofthe elongate body 1402. In the present example, the three or moresurfaces 1412 of the elongate body 1402 help to form the second portion1472 of the elongate body 1402. If desired, the elongate body 1402 canincludes a serpentine portion proximal to the one or more electrodes1414.

Referring now to FIG. 15A, there is shown an additional example of acatheter 1582 according to the present disclosure. The catheter 1582 caninclude the features and components of the catheters described above inconnection with FIGS. 12A-12D, 14A and/or 14B, a discussion of which isnot repeated but the element numbers are included in FIG. 15A with theunderstanding that the discussion of these elements is implicit.

The catheter 1582 includes an elongate body 1502 having a peripheralsurface 1536 and a longitudinal center axis 1508 extending between afirst end 1504 and a second end 1506. The elongate body 1502 includes asurface 1552 defining a deflection lumen 1554, where the deflectionlumen 1554 includes a first opening 1556 and a second opening 1558 inthe elongate body 1502. The catheter 1582 further includes an inflatableballoon 1534 on the peripheral surface 1536 of the elongate body 1502,the inflatable balloon 1534 having a balloon wall 1538 with an interiorsurface 1540 that along with a portion 1542 of the peripheral surface1536 of the elongate body 1502 defines a fluid tight volume 1544, suchas previously discussed herein. An inflation lumen 1546 extends throughthe elongate body 1502, where the inflation lumen 1546 has a firstopening 1548 into the fluid tight volume 1544 of the inflatable balloon1534 and a second opening 1550 proximal to the first opening 1548 toallow for a fluid (e.g., liquid or gas) to move in and out of the fluidtight volume 1544 to inflate and deflate the balloon 1534.

One or more electrodes 1514 are on the elongate body 1502, where thesecond opening 1558 of the deflection lumen 1554 is opposite the one ormore electrodes 1514 on the elongate body 1502. The catheter 1582further includes an elongate deflection member 1560, as discussedherein, where the elongate deflection member 1560 extends through thesecond opening 1558 of the deflection lumen 1554 in a direction oppositethe one or more electrodes 1514 on one surface of the elongate body1502. The catheter 1582 also includes conductive elements 1516 thatextend through and/or along the elongate body 1502, where the conductiveelements 1516 conduct electrical current to combinations of the one ormore electrodes 1514.

The catheter 1582 further includes a surface 1524 defining a guide-wirelumen 1526 that extends through and/or along the elongate body 1502. Asillustrated, the guide-wire lumen 1526 is concentric relative to thelongitudinal center axis 1508. As discussed herein, the guide-wire lumen1526 could also be eccentric relative to longitudinal center axis 1508of the elongate body 1508. Such examples are discussed herein, where theguide-wire lumen 1526 can have a wall thickness taken perpendicularly tothe longitudinal center axis 1508 that is greater than a wall thicknessof a remainder of the catheter 1582 taken perpendicularly to thelongitudinal center axis 1508. The catheter 1582 can also include aserpentine portion of the elongate body 1502 proximal to the one or moreelectrodes 1514.

Referring now to FIG. 15B, there is shown an additional example of acatheter 1582. The catheter 1582 can include the features and componentsdescribed above in connection with FIGS. 12A-12D, 14A, 14B and/or 15A, adiscussion of which is not repeated but the element numbers are includedin FIG. 15B with the understanding that the discussion of these elementsis implicit.

The catheter 1582 includes an elongate body 1502 having a peripheralsurface 1536 and a longitudinal center axis 1508 extending between afirst end 1504 and a second end 1506. The elongate body 1502 includes asurface 1552 defining a deflection lumen 1554, where the deflectionlumen 1554 includes a first opening 1556 and a second opening 1558 inthe elongate body 1502. The catheter 1582 further includes an inflatableballoon 1534 on the peripheral surface 1536 of the elongate body 1502,the inflatable balloon 1534 having a balloon wall 1538 with an interiorsurface 1540 that along with a portion 1542 of the peripheral surface1536 of the elongate body 1502 defines a fluid tight volume 1544, asdiscussed herein. An inflation lumen 1546 extends through the elongatebody 1502, where the inflation lumen 1546 has a first opening 1548 intothe fluid tight volume 1544 of the inflatable balloon 1534 and a secondopening 1550 proximal to the first opening 1548 to allow for a fluid(e.g., gas or liquid) to move in and out of the fluid tight volume 1544to inflate and deflate the balloon 1534.

One or more electrodes 1514 are on the elongate body 1502, where thesecond opening 1558 of the deflection lumen 1554 is opposite the one ormore electrodes 1514 on the elongate body 1502. As illustrated, theelongate body 1502 has three or more surfaces 1512 defining a convexpolygonal cross-sectional shape taken perpendicularly to thelongitudinal center axis 1508. The one or more electrodes 1514 are onone surface of the three or more surfaces 1512 of the elongate body1502, such as discussed previously herein.

The catheter 1582 further includes an elongate deflection member 1560,where the elongate deflection member 1560 extends through the secondopening 1558 of the deflection lumen 1554 in a direction opposite theone or more electrodes 1514 on one surface of the elongate body 1502.The catheter 1582 also includes conductive elements 1516 that extendthrough and/or along the elongate body 1502, where the conductiveelements 1516 conduct electrical current to combinations of the one ormore electrodes 1514.

The catheter 1582 further includes a surface 1524 defining a guide-wirelumen 1526 that extends through and/or along the elongate body 1502. Asillustrated, the guide-wire lumen 1526 is concentric relative to thelongitudinal center axis 1508. As discussed herein, the guide-wire lumen1526 could also be eccentric relative to longitudinal center axis 1508of the elongate body 1502. Such examples are discussed herein, where theguide-wire lumen 1526 can have a wall thickness taken perpendicularly tothe longitudinal center axis 1508 that is greater than a wall thicknessof a remainder of the catheter 1582 taken perpendicularly to thelongitudinal center axis 1508. The catheter 1582 can also include aserpentine portion of the elongate body 1502 proximal to the one or moreelectrodes 1514.

Referring now to FIG. 16, there is shown an additional example of acatheter 1684. The catheter 1684 can include the features and componentsof the catheters described above in connection with FIGS. 12A-12D, 14A,14B, 15A and/or 15B, a discussion of which is not repeated but theelement numbers are included in FIG. 16 with the understanding that thediscussion of these elements is implicit.

The catheter 1684 includes an elongate body 1602 having a peripheralsurface 1636 and a longitudinal center axis 1608 extending between afirst end 1604 and a second end 1606. The catheter 1684 further includesan inflatable balloon 1634 on the peripheral surface 1636 of theelongate body 1602, the inflatable balloon 1634 having a balloon wall1638 with an interior surface 1640 that along with a portion 1642 of theperipheral surface 1636 of the elongate body 1602 defines a fluid tightvolume 1644, as discussed herein. An inflation lumen 1646 extendsthrough the elongate body 1602, where the inflation lumen 1646 has afirst opening 1648 into the fluid tight volume 1644 of the inflatableballoon 1634 and a second opening 1650 proximal to the first opening1648 to allow for a fluid (e.g., gas or liquid) to move in and out ofthe fluid tight volume 1644 to inflate and deflate the balloon 1634.

The catheter 1682 includes a surface 1624 defining a guide-wire lumen1626 that extends through and/or along the elongate body 1602. Asillustrated, the guide-wire lumen 1626 is concentric relative to thelongitudinal center axis 1608. As discussed herein, the guide-wire lumen1626 could also be eccentric relative to longitudinal center axis 1608of the elongate body 1608. Such examples are discussed herein, where theguide-wire lumen 1626 can have a wall thickness taken perpendicularly tothe longitudinal center axis 1608 that is greater than a wall thicknessof a remainder of the catheter 1682 taken perpendicularly to thelongitudinal center axis 1608. The catheter 1682 can also include aserpentine portion of the elongate body 1602 proximal to the one or moreelectrodes 1614.

The elongate body 1602 of the catheter 1684 further includes a surface1686 defining an electrode lumen 1688. The electrode lumen 1688 includesa first opening 1690 and a second opening 1692 in the elongate body1602. The catheter 1684 also includes an elongate electrode member 1694,where the elongate electrode member 1694 retractably extends through thefirst opening 1690 of the electrode lumen 1688 of the elongate body1602. The electrode lumen 1688 has a size (e.g., a diameter) sufficientto allow the elongate electrode member 1694 to pass through theelectrode lumen 1688 to that the elongate electrode member 1694 canretractably extend through the first opening 1690 of the electrode lumen1688 of the elongate body 1602. The elongate electrode member 1694 canretractably extend through the first opening 1690 of the electrode lumen1688 of the elongate body 1602 from pressure (e.g., compression ortension) applied by the user (e.g., clinician or professional) throughthe elongate electrode member 1694 proximal to the second opening 1692in the elongate body 1608. For the various examples, the elongateelectrode member 1694 is formed of a flexible polymeric material.Examples of such flexible polymeric material include, but are notlimited to, those flexible materials described herein.

The elongate electrode member 1694 includes one or more electrodes 1696and conductive elements 1698 extending through the electrode lumen 1688.As illustrated, the one or more electrodes 1696 are on the surface 1601of the elongate electrode member 1694. Conductive elements 1698 extendthrough the elongate electrode member 1694, where the conductiveelements 1698 can be used, such as discussed herein, to conductelectrical current to combinations of the one or more electrodes 1696.Each of the one or more electrodes 1696 is coupled to a correspondingconductive element 1698.

The conductive elements 1698 may be electrically isolated from eachother and extend through the elongate electrode member 1694 from eachrespective electrode 1696 through the second end 1692 of the electrodelumen 1688. The conductive elements 1698 terminate at a connector port,where each of the conductive elements 1698 can be releasably coupled toa stimulation system, as discussed herein. It is also possible that theconductive elements 1698 are permanently coupled to the stimulationsystem (e.g., not releasably coupled). The stimulation system can beused to conduct electrical current or electrical pulses to combinationsof the one or more electrodes 1694 via the conductive elements 1698. Theone or more electrodes 1696 are electrically isolated from one another,where the elongate electrode member 1694 is formed of an electricallyinsulating material.

The number and the configuration of the one or more electrodes 1696 onthe elongate electrode member 1694 can vary in differentexampleexamples. For example, as illustrated, the one or more electrodes1696 can be configured as an array of electrodes, where the number ofelectrodes and their relative position to each other can vary dependingupon the desired implant location. As discussed herein, the one or moreelectrodes 1696 can be configured to allow for electrical current to bedelivered from and/or between different combinations of the one or moreelectrodes 1696. So, for example, the electrodes in the array ofelectrodes can have a repeating pattern where the electrodes are equallyspaced from each other. Other patterns are possible, where such patternscan either be repeating patterns or random patterns.

As illustrated, the one or more electrodes 1696 have an exposed face1603. The exposed face 1603 of the electrode 1696 provides theopportunity for the electrode 1696, when implanted (temporarily or foran extended duration of time) in the patient, to be placed intoproximity and/or in contact with the vascular tissue of the patient, asopposed to facing into the volume of blood in the artery. To accomplishthis, the one or more electrodes 1696 can be located on only one side ofthe elongate electrode member 1694 (as illustrated in FIG. 16). Thisallows the one or more electrodes 1696 to be brought into contact withthe vascular luminal surface (e.g., a posterior surface of the mainpulmonary artery and/or one or both of the pulmonary arteries). As theone or more electrodes 1696 are located on only one side of the elongateelectrode member 1694, the electrodes 1696 can be placed into directproximity to and/or in contact with the tissue of any combination of themain pulmonary artery, the left pulmonary artery and/or the rightpulmonary artery.

The exposed face 1603 of the one or more electrodes 1696 can have avariety of shapes, as discussed herein (e.g., a partial ringconfiguration, where each of the one or more electrodes 1696 ispositioned to face away from the elongate body 1602). The exposed face1603 of the electrodes 1696 can also include one or more anchorstructures. Examples of such anchor structures include hooks that canoptionally include a barb.

As generally illustrated, the elongate electrode member 1694 can beadvanced through the electrode lumen 1688 so that the elongate electrodemember 1694 extends laterally away from the elongate body 1608. Theelongate electrode member 1694 can be of a length and shape that allowsthe elongate electrode member 1694 to be extended a distance sufficientfrom the elongate body 1608 to bring the one or more electrodes 1696into contact with the vascular luminal surface (e.g., a posteriorsurface of the main pulmonary artery and/or one or both of the pulmonaryarteries).

As illustrated in FIG. 16, the elongate electrode member 1694 forms aloop 1605 that extends away from the peripheral surface 1636 of theelongate body 1602. The loop 1605 can have a variety of configurationsrelative the longitudinal axis 1608 of the elongate body 1602. Forexample, as illustrated in FIG. 16, the elongate electrode member 1692forming the loop 1605 is in a plane 1607 that is co-linear with thelongitudinal center axis 1608 of the elongate body 1602.

The catheter 1684 further includes an elongate deflection member 1660,as previously discussed. As discussed herein, pressure is applied to thedeflection member 1660 to move the first end 1663 of the deflectionmember 1660 towards the first opening 1656 of the deflection lumen 1654.The pressure, in addition to moving the first end 1663 of the deflectionmember 1660 towards the first opening 1656, also causes the second end1665 of the deflection member 1660 to extend from the second opening1658. As generally illustrated, the elongate deflection member 1660 canbe advanced through the deflection lumen 1654 so that elongatedeflection member 1660 extends laterally away from the one or moreelectrodes 1696 on the elongate electrode member 1694. The elongatedeflection member 1660 can be of a length and shape that allows theelongate deflection member 1660 to be extended a distance sufficient tohelp bring the one or more electrodes 1696 into contact with thevascular luminal surface (e.g., a posterior surface of the mainpulmonary artery and/or one or both of the pulmonary arteries) with avariety of pressures. Optionally, the elongate deflection member 1660can be configured to include one or more of the electrodes.

The catheter 1684 shown in FIG. 16 can be positioned in the mainpulmonary artery and/or one or both of the left and right pulmonaryarteries of the patient, such as described herein. To accomplish this, apulmonary artery guide catheter is introduced into the vasculaturethrough a percutaneous incision and guided to the right ventricle (e.g.,using a Swan-Ganz catheterization approach). For example, the pulmonaryartery guide catheter can be inserted into the vasculature via aperipheral vein of the arm, neck or chest (e.g., as with a peripherallyinserted central catheter). Changes in a patient's electrocardiographyand/or pressure signals from the vasculature can be used to guide andlocate the pulmonary artery guide catheter within the patient's heart.Once in the proper location, a guide wire can be introduced into thepatient via the pulmonary artery guide catheter, where the guide wire isadvanced into the main pulmonary artery and/or one of the pulmonaryarteries. Using the guide-wire lumen 1626, the catheter 1684 can beadvanced over the guide wire so as to position the catheter 1684 in themain pulmonary artery and/or one or both of the right and left pulmonaryarteries of the patient. Various imaging modalities can be used inpositioning the guide wire of the present disclosure in the mainpulmonary artery and/or one of the right and left pulmonary arteries ofthe patient. Such imaging modalities include, but are not limited to,fluoroscopy, ultrasound, electromagnetic, and electropotentialmodalities.

Using a stimulation system, such as the stimulation systems discussedherein, stimulation electrical energy (e.g., electrical current orelectrical pulses) can be delivered across combinations of one or moreof the electrodes 1696. It is possible for the patient's cardiacresponse to the stimulation electrical energy to be monitored andrecorded for comparison to other subsequent tests. It is appreciatedthat for any of the catheters discussed herein any combination ofelectrodes, including reference electrodes (as discussed herein)positioned within or on the patient's body, can be used in providingstimulation to and sensing cardiac signals from the patient.

Referring now to FIG. 17, there is shown an additional example of acatheter 1784. The catheter 1784 can include the features and componentsof the catheters described above in connection with FIGS. 12A-12D, 14A,14B, 15A, 15B and/or 16, a discussion of which is not repeated but theelement numbers are included in FIG. 17 with the understanding that thediscussion of these elements is implicit. The catheter 1784 illustratesan example in which the elongate electrode member 1794 forms a loop 1705in a plane 1707 that is perpendicular to the longitudinal center axis ofthe elongate body. More than one of the elongate electrode members canbe used with a catheter, in accordance with several examples.

Referring now to FIGS. 18A through 18C, there are shown perspectiveviews of an example catheter 1830 that is suitable for performingcertain methods of the present disclosure. The catheter 1830 includes anelongate catheter body 1832 having a proximal or first end 1834 and adistal or second end 1836. The elongate catheter body 1832 also includesan outer or peripheral surface 1838 and an interior surface 1840defining a lumen 1842 (shown with a broken line) that extends betweenthe first end 1834 and the second end 1836 of the elongate catheter body1832.

The catheter 1830 further includes a plurality of electrodes 1844positioned along the peripheral surface 1838 of the elongate catheterbody 1832. In some examples, the electrodes 1844 are proximate to adistal end 1836 of the catheter 1830. Conductive elements 1846 extendthrough and/or along the elongate body 1832, where the conductiveelements 1846 can be used, as discussed herein, to conduct electricalpulses to combinations of the plurality of electrodes 1844. Each of theplurality of electrodes 1844 is coupled (e.g., electrically coupled) toa corresponding conductive element 1846. The conductive elements 1846are electrically isolated from each other and extend through theelongate body 1832 from each respective electrode 1844 through the firstend 1834 of the elongate body 1832. The conductive elements 1846terminate at a connector port, where each of the conductive elements1846 can be releasably coupled to a stimulation system. It is alsopossible that the conductive elements 1846 are permanently coupled tothe stimulation system (e.g., not releasably coupled). As discussed morefully herein, the stimulation system can be used to provide stimulationelectrical pulses that are conducted through the conductive elements1846 and delivered across combinations of the plurality of electrodes1844. Other positions and configurations of electrodes are alsopossible. PCT Patent App. Nos. PCT/US2015/031960, PCT/US2015/047770, andPCT/US2015/047780 are incorporated herein by reference in theirentirety, and more specifically the electrodes (e.g., electrodes ondeployable filaments) and electrode matrices disclosed therein areincorporated herein by reference.

The elongate body 1832 may comprise (e.g., be at least partially formedof) an electrically insulating material. Examples of such insulatingmaterial can include, but are not limited to, medical gradepolyurethanes, such as polyester-based polyurethanes, polyether-basedpolyurethanes, and polycarbonate-based polyurethanes; polyamides,polyamide block copolymers, polyolefins such as polyethylene (e.g., highdensity polyethylene); and polyimides, among others.

The catheter 1830 optionally includes an anchor 1848. The anchor 1848includes struts 1850 that form an open framework, where the struts 1850extend laterally or radially outwardly from the elongate body 1832(e.g., from a peripheral surface 1838 of the elongate body 1832) to atleast partially define a peripheral surface 1852 configured to engagevascular tissue (e.g., configured to appose sidewalls forming the lumenof the right pulmonary artery and/or the left pulmonary artery). FIGS.18A through 18C show the anchor 1848 positioned between the second end1836 and the plurality of electrodes 1844 of the elongate catheter body1832. It is also possible that the anchor 1848 can be positioned betweenthe plurality of electrodes 1844 and the second end 1836 of the elongatecatheter body 1832. In some examples, the anchor 1848 can inhibit orprevent at least a portion of the catheter 1830 (e.g., the portion 1854,a portion comprising the electrodes 1844) from extending intovasculature smaller than the expanded struts 1850. For example, withreference to FIG. 19, the plurality of electrodes 1944 can be proximalto the branch point 1976 such that portions of the catheter 1930proximal to the anchor 1948 do not extend into the two additionalarteries 1978. If the sensor 1966 is distal to the anchor 1948,interaction of the anchor 1948 and the branch point 1976 may ensure thatthe sensor 1966 is in a pulmonary artery branch vessel 1978.

The struts 1850 can have a cross-sectional shape and dimension thatallow for the struts 1850 to provide a radial force sufficient to holdthe catheter 1830 at the implant location within the pulmonary arteryunder a variety of situations, as discussed herein. The struts 1850 canbe formed of a variety of materials, such as a metal, metal alloy,polymer, etc. Examples of such metals or metal alloys include surgicalgrade stainless steel, such as austenitic 316 stainless among others,and the nickel and titanium alloy known as Nitinol. Other metals and/ormetal alloys, as are known or may be developed, can be used.

A portion 1854 of the elongate catheter body 1832, for example thatincludes one, some, none, or all the plurality of electrodes 1844, cancurve in a predefined radial direction (e.g., anterior, posterior,inferior, superior, and combinations thereof), for example when placedunder longitudinal compression. To provide the curve in the portion1854, the elongate catheter body 1832 can be pre-stressed and/or thewall can have thicknesses that allow for the elongate catheter body 1832to curve in the predefined radial direction, for example when placedunder longitudinal compression. In addition, or alternatively,structures such as coils or a helix of wire having different turns perunit length, a hypotube having varying kerf spacing, etc. can be locatedin, around, and/or along the elongate catheter body 1832 in the portion1854. One or more of these structures can be used to allow thelongitudinal compression to create the curve in the predefined radialdirection in the portion 1854. To achieve the longitudinal compression,the anchor 1848 can be deployed in the vasculature of the patient (e.g.,in the pulmonary artery), where the anchor 1848 provides a location orpoint of resistance against the longitudinal movement of the elongatebody 1832. As such, this allows a compressive force to be generated inthe elongate catheter body 1832 sufficient to cause the portion 1854 ofthe elongate catheter body 1832, for example along which the pluralityof electrodes 1844 are present, to curve in the predefined radialdirection.

FIG. 18D provides an illustration of the portion 1854 of the elongatecatheter body 1832 curved in a predefined radial direction when placedunder longitudinal compression. The catheter 1830 illustrated in FIG.18D is similar to the catheter 1830 shown in FIG. 18A and is describedherein, although other catheters having similar features can also beused. In the catheter 1830 illustrated in FIG. 18D, a sensor 1866 isproximal to the electrodes 1844. When the electrodes 1844 are in theright pulmonary artery 206, the sensor 1866 can be in the pulmonarytrunk 202, for example. If the sensor 1866 is more proximal, the sensor1866 can be in the right ventricle, the superior vena cava, etc.Positioning the sensor 1866 proximal along the catheter 1830 can allowthe sensor 1866 to be in a location different than the location of theelectrode 1844 without positioning the sensor 1866 separate frompositioning the electrode 1844. As illustrated in FIG. 18D, the catheter1830 has been at least partially positioned within the main pulmonaryartery 202 of a patient's heart 200, where the anchor 1848 is located inthe lumen of the right pulmonary artery 206. From this position, alongitudinal compressive force applied to the elongate catheter body1832 can cause the portion 1854 of the elongate catheter body 1832,along with at least some of the plurality of electrodes 1844 in thisexample, to curve in the predefined radial direction, superior in thisexample. The curvature allows (e.g., causes) the plurality of electrodes1844 to extend towards and/or touch the luminal surface of the mainpulmonary artery 202 and/or right pulmonary artery 206. Preferably, theplurality of electrodes 1844 are brought into position and/or contactwith the luminal surface of the main pulmonary artery 202 and/or rightpulmonary artery 206.

In some examples, the elongate catheter body 1832 of the catheter 1830can use the lumen 1842 that extends from the first end 1834 towards thesecond end 1836 to provide a curve in a predefined radial direction. Forexample, the catheter 1830 can include a shaping wire 1857 having afirst end 1859 and a second end 1861, as illustrated in FIG. 18A. Theshaping wire 1857 can be bent and retain a desired shape that, uponinsertion into the lumen 1842, can at least partially provide thecatheter 1830 with a curve. The lumen 1842 has a size (e.g., a diameter)sufficient to allow the shaping wire 1857 to pass through the lumen 1842with the second end 1861 of the shaping wire 1857 proximate to thesecond end 1836 of the elongate catheter body 1832 so that the bentportion 1863 of the shaping wire 1857 imparts a curve into the portion1854 of the elongate catheter body 1832, allowing the plurality ofelectrodes 1844 to extend towards and/or touch the luminal surface ofthe main pulmonary artery. In some examples the shaping wire 1857 cancomplement the portion 1854. In some examples, the shaping wire 1857 canbe used in place of the portion 1854 (e.g., if the catheter 1830 doesnot include the portion 1854 or by not imparting the longitudinalcompressive force). In some examples, the shaping wire 1857 can be usedto impart a curve that is contrary to the curve that the portion 1854would cause if a compressive force was applied. In some examples, theshaping wire 1857 may be inserted into the lumen 1842 in any rotationalorientation such that a curve can be imparted in any desired radialdirection, for example depending on the position of the anchor 1848. Theshaping wire 1857 can allow formation of a curve even if the catheter1830 does not include an anchor 1848, for example because the catheterbody 1832 can conform to the shape of the shaping wire regardless ofwhether the catheter 1830 is anchored to the vasculature. In someexamples, insertion of the shaping wire 1857 into the lumen 1842 impartsa curve to the portion 1854 such that at least one of the electrodes1844 apposes a superior/posterior sidewall of the pulmonary artery.

In some examples, a neuromodulation system comprises a catheter 1830 anda shaping wire 1857. The catheter 1830 comprises a catheter body 1832,an electrode 1844, and a sensor 1866. The catheter body 1832 comprises aproximal end 1834, a distal end 1836, a lumen 1842 extending from theproximal end 1834 towards the distal end 1836 (e.g., at least distal tothe electrode 1844), and an outer surface 1838. The electrode 1844 is onthe outer surface 1838. The electrode 1844 is configured to deliver anelectrical signal to a pulmonary artery of a patient (e.g., to providecalibration and/or therapeutic stimulation to a nerve proximate thepulmonary artery).

The shaping wire 1857 comprises a material that is configured to causethe catheter body 1832 to bend. For example, the radial force of theshaping wire 1857 may be greater than the forces that keep the catheterbody 1832 in a generally straight configuration. In some examples, theshaping wire 1857 comprises a shape memory material (e.g., nitinol,chromium cobalt, copper aluminum nickel, etc.) or a resilient material(e.g., stainless steel, etc.). For example, the shaping wire 1857 may bestressed to a straight wire in a proximal portion of the catheter 1830,but in a portion of the catheter 1830 to be bent, which may be, forexample, weaker that the proximal portion of the catheter 1830, theshaping wire 1857 can revert to the unstressed curved shape within thecatheter 1830. In some examples in which the shaping wire 1857 comprisesa shape memory material, the shaping wire 1857 may utilize thermal shapememory. For example, the shaping wire 1857 may be in a substantiallystraight shape until cold or warm fluid (e.g., saline) causes reversionto the curved shape. In some such examples, the entire catheter 1830 maybe bendable by the shaping wire 1857, but the temperature change iseffected once the shaping wire 1857 is in a desired longitudinal and/orradial position. In some examples, the entire catheter 1830 may bebendable by the shaping wire 1857. For example, the curve may propagatealong the length of the catheter 1830 until the curve is in a desiredposition.

The shaping wire 1857 has a diameter or cross-sectional dimension lessthan the diameter or cross-sectional dimension of the lumen 1842. Forexample, if the catheter body 1832 is 20 French (Fr) (approx. 6.67millimeters (mm)), the lumen 1842 may be 18 Fr (approx. 6 mm) and theshaping wire 1857 may be 16 Fr (approx. 5.33 mm). The shaping wire 1857may be, for example 1 Fr less than the lumen 1842 (e.g., for more radialforce than if 2 Fr less) or 2 Fr less than the lumen 1842 (e.g., forless friction during navigation than if 1 Fr less). The shaping wire1857 may be, for example 2 Fr less than the catheter body 1832 (e.g., ifthe lumen 1842 is 1 Fr less than the catheter body 1832) or 4 Fr lessthan the catheter body 1832 (e.g., providing flexibility for the size ofthe lumen 1842 to be 1 or 2 Fr less than the catheter body). Shapingwire sizes other than on a French catheter scale are also possible(e.g., having a diameter less than a diameter of the lumen 1842 by about0.05 mm, 0.1 mm, by about 0.2 mm, by about 0.25 mm, by about 0.5 mm,ranges between such values etc.).

The sensor 1866 is on the outer surface 1838. The sensor 1866 isconfigured to sense a heart activity property (e.g., a non-electricalheart activity property such as a pressure property, an accelerationproperty, an acoustic property, a temperature, and a blood chemistryproperty) from a location within in vasculature of the patient. Thelocation may be different than the pulmonary artery in which theelectrode 1844 is positioned. For example, if the electrode 1844 is inthe right pulmonary artery, the location of the sensor 1866 may be inthe pulmonary trunk, a pulmonary artery branch vessel, the rightventricle, the ventricular septal wall, the right atrium, the septalwall of the right atrium, the superior vena cava, the inferior venacava, the left pulmonary artery, the coronary sinus, etc. The shapingwire 1857 is configured to be positioned in the lumen 1842 of thecatheter body 1832. The shaping wire comprising a bent portion 1863. Forexample, from a proximal end 1859 to a distal end 1861, the shaping wire1857 may be substantially straight in a substantially straight portion,then have a bent portion 1863 extending away from a longitudinal axis ofthe straight portion. The bent portion 1863 may include one bend or aplurality of bends (e.g., two bends (as illustrated in FIG. 18A), threebends, or more bends). The shaping wire 1857 may optionally compriseanother substantially straight portion after the bent portion, which mayhave a longitudinal axis that is substantially aligned with thelongitudinal axis of the proximal straight portion. When the shapingwire 1857 is inserted in the lumen 1842 of the catheter body 1832, thecatheter body 1832 comprises a curved portion 1854 corresponding to thebent portion 1863 of the shaping wire 1857. For example, the catheterbody 1832, or the portion 1854, may comprise a material that can be bentdue to pressure or stress applied to the lumen 1842 or interior surface1840 of the catheter body 1832. In some examples, insertion of theshaping wire 1857 into the lumen 1842 imparts a curve to the portion1854 such that at least one of the electrodes 1844 apposes asuperior/posterior sidewall of the pulmonary artery.

FIGS. 18A through 18C further illustrate an example delivery catheter1856 that can be used in conjunction with the catheter 1830. Thedelivery catheter 1856 can be a Swan-Ganz type pulmonary arterycatheter, as are known, that includes a surface 1858 defining a lumen1860 sized sufficiently to receive, store, and deploy the catheter 1830.As illustrated, the delivery catheter 1856 includes a reversiblyinflatable balloon 1862 in fluid communication with a balloon inflationlumen that extends from a proximal or first end 1864 of the deliverycatheter 1856 (e.g., where the inflation lumen can be to an inflationfluid source) to the interior volume of the reversibly inflatableballoon 1862.

The catheter 1830 also includes a first sensor 1866. As illustrated inFIGS. 18A through 18C, the first sensor 1866 can be positioned at anumber of different locations along the catheter 1830. In FIG. 18A, thefirst sensor 1866 is positioned on the elongate catheter body 1832distal to the anchor 1848. A sensor 1866 that is proximate to the distalend 1836 of the catheter 1830 may also or alternatively be useful fornavigation of the catheter 1830, for example to determine an anatomicallocation during floating a balloon such as with a Swan-Ganz catheter. InFIG. 18B, the first sensor 1866 is positioned on or between one of thestruts 1850 of the anchor. In FIG. 18C, the first sensor 1866 ispositioned proximal to both the anchor 1848 and the plurality ofelectrodes 1844. In FIG. 18D, the first sensor 1866 is positionedproximal enough that the first sensor 1866 can be in a location of thevasculature different than the electrodes 1844. In some examples, thecatheter 1830 comprises a plurality of sensors 1866 at more than one ofthe positions illustrated in FIGS. 18A through 18C and/or otherpositions.

The catheter 1830 further includes a sensor conductor 1868. The firstsensor 1866 is coupled to the sensor conductor 1868 and is isolated fromthe conductive elements 1846 and electrodes 1844. The coupling may beelectrical, optical, pressure, etc. The sensor conductor 1868 extendsthrough the elongate body 1832 from the first sensor 1866 through thefirst end 1834 of the elongate body 1832. The sensor conductor 1868terminates at a connector port that can be used, for example, toreleasably couple the first sensor 1866 to the stimulation system, asdiscussed herein.

The first sensor 1866 can be used to sense one or more activity property(e.g., electrical and/or non-electrical heart activity properties). Insome examples, the property can be measured in response to one or moreelectrical pulses delivered using the plurality of electrodes 1844.Examples of non-electrical heart activity properties include, but arenot limited to, one or more of a pressure property, an accelerationproperty, an acoustic property, a temperature, and a blood chemistryproperty measured from within the vasculature of the heart. Asappreciated, two or more of the non-electrical heart activity propertiescan be measured by using more than one sensor on the catheter 1830.

For use in detecting a pressure property, the first sensor 1866 can be apressure sensing transducer, for example such as disclosed in U.S. Pat.No. 5,564,434 (e.g., configured to detect changes in blood pressure,atmospheric pressure, and/or blood temperature and to provide modulatedpressure and/or temperature related signals), incorporated by referenceherein in its entirety. For use in detecting an acceleration property,the first sensor 1866 can be an acceleration sensor, for example such asdisclosed in U.S. Patent Pub. No. 2004/0172079 to Chinchoy (e.g.,configured to generate a signal proportional to acceleration of a heartmuscle or wall such as a coronary sinus wall, septal wall, or ventriclewall) or U.S. Pat. No 7,092,759 to Nehls et al. (e.g., configured togenerate a signal proportional to acceleration, velocity, and/ordisplacement of a heart muscle or wall such as a coronary sinus wall,septal wall, or ventricle wall), each of which is incorporated byreference herein in its entirety. For use in detecting an acousticproperty, the first sensor 1866 can be a piezoelectric transducer (e.g.,a microphone) or a blood flow sensor, for example such as disclosed inU.S. Pat. No. 6,754,532 (e.g., configured to measure a velocity of bloodto estimate blood flow volume), which is incorporated by referenceherein in its entirety. For use in detecting a temperature, the firstsensor 1866 can be a temperature sensor, for example such as disclosedin U.S. Pat. No. 5,336,244 (e.g., configured to detect variations inblood temperature and/or oxygen concentration indicative of themechanical pumping action of the heart) and/or U.S. Patent Pub. No.2011/0160790 (e.g., configured to sense temperature and to produce atemperature signal), each of which is incorporated by reference hereinin its entirety. For use in detecting a blood chemistry properties, thefirst sensor 1866 can be an oxygen sensor or a glucose sensor, forexample such as disclosed in U.S. Pat. No. 5,213,098 (e.g., configuredto sense blood oxygen saturation levels that vary with cardiac muscleoxygen uptake) and/or U.S. Patent Pub. No. 2011/0160790 (e.g.,configured to measure oxygen and/or glucose concentration in blood andto produce an oxygen and/or glucose signal), each of which isincorporated by reference herein in its entirety. Other types of sensorscan also be used for the first sensor 1866, other sensors describedherein, and the like.

The catheter 1830 shown in FIGS. 18A through 18C can be positioned inthe right pulmonary artery, the left pulmonary artery, or the pulmonarytrunk of the patient, for example as described herein. To accomplishthis, the delivery catheter 1856 with the catheter 1830 housed thereincan be introduced into the vasculature through a percutaneous incision,and guided to the right ventricle. For example, the delivery catheter1856 can be inserted into the vasculature via a peripheral vein of theneck or chest (e.g., as with a Swan-Ganz catheter). Changes in apatient's electrocardiography and/or pressure signals from thevasculature can be used to guide and locate the pulmonary arterycatheter within the patient's heart. Once in the proper location, aguide wire can be introduced into the patient via the pulmonary arteryguide catheter, where the guide wire is advanced into the desiredpulmonary artery (e.g., the right pulmonary artery). The deliverycatheter 1856 with the catheter 1830 housed therein can be advanced overthe guide wire so as to position the catheter 1830 in the desiredpulmonary artery of the patient (e.g., the right pulmonary artery or theleft pulmonary artery), for example as described herein. Various imagingmodalities can be used in positioning the guide wire of the presentdisclosure in the pulmonary artery of the patient. Such imagingmodalities include, but are not limited to, fluoroscopy, ultrasound,electromagnetic, and electropotential modalities.

When the catheter 1830 is positioned in the right pulmonary artery orthe left pulmonary artery and the sensor 1866 is configured to beproximal to the electrodes 1844, a distance between the electrodes 1844(e.g., from the proximal-most electrode 1844) and the sensor 1866 may bebetween about 1 cm and about 5 cm (e.g., about 1 cm, about 2 cm, about 3cm, about 4 cm, about 5 cm, ranges between such values, etc.), in whichcase the sensor 1866 can reside in the pulmonary trunk, between about 8cm and about 20 cm (e.g., about 8 cm, about 9 cm, about 10 cm, about 11cm, about 12 cm, about 13 cm, about 14 cm, about 16 cm, about 18 cm,about 20 cm, ranges between such values, etc.), in which case the sensor1866 can reside in the right ventricle, between about 16 cm and about 27cm (e.g., about 16 cm, about 17 cm, about 18 cm, about 19 cm, about 20cm, about 21 cm, about 22 cm, about 23 cm, about 25 cm, about 27 cm,ranges between such values, etc.), in which case the sensor 1866 canreside in the right atrium, or between about 21 cm and about 33 cm(e.g., about 21 cm, about 23 cm, about 25 cm, about 26 cm, about 27 cm,about 28 cm, about 29 cm, about 30 cm, about 31 cm, about 32 cm, about33 cm, ranges between such values, etc.), in which case the sensor 1866can reside in the superior vena cava.

When the catheter 1830 is positioned in the pulmonary trunk and thesensor 1866 is configured to be distal to the electrodes 1844, adistance between the electrodes 1844 (e.g., from the distal-mostelectrode 1844) and the sensor 1866 may be between about 1 cm and about5 cm (e.g., about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm,ranges between such values, etc.), in which case the sensor 1866 canreside in the right pulmonary artery or the left pulmonary artery. Whenthe catheter 1830 is positioned in the pulmonary trunk and the sensor1866 is configured to be proximal to the electrodes 1844, a distancebetween the electrodes 1844 (e.g., from the proximal-most electrode1844) and the sensor 1866 may be between about 3 cm and about 19 cm(e.g., about 3 cm, about 5 cm, about 6 cm, about 7 cm, about 8 cm, about9 cm, about 10 cm, about 12 cm, about 15 cm, about 19 cm, ranges betweensuch values, etc.), in which case the sensor 1866 can reside in theright ventricle, between about 11 cm and about 26 cm (e.g., about 11 cm,about 13 cm, about 15 cm, about 16 cm, about 17 cm, about 18 cm, about19 cm, about 20 cm, about 22 cm, about 24 cm, about 26 cm, rangesbetween such values, etc.), in which case the sensor 1866 can reside inthe right atrium, or between about 16 cm and about 32 cm (e.g., about 16cm, about 18 cm, about 20 cm, about 22 cm, about 24 cm, about 25 cm,about 26 cm, about 27 cm, about 28 cm, about 30 cm, about 32 cm, rangesbetween such values, etc.), in which case the sensor 1866 can reside inthe superior vena cava.

FIG. 19 provides a perspective view of a catheter 1930 positioned in theheart 200 of a subject (e.g., patient), where one or more of a pluralityof electrodes 1944 are contacting the posterior 221 and/or superiorsurface 223 of the right pulmonary artery 206 (e.g., at a position thatis superior to the branch point 207). FIG. 19 further illustrates theexample in which the first sensor 1966 is positioned distal from theanchor 1948. As illustrated, the pulmonary trunk 202 has a diameter 1970taken across a plane 1972 substantially perpendicular to both the leftlateral plane 220 and the right lateral plane 216. In a preferredexample, the plurality of electrodes 1944 of the catheter 1930 ispositioned in an area 1974 that extends distally no more than aboutthree times the diameter 1970 of the pulmonary trunk 202 to the right ofthe branch point 207. This area 1974 is shown with cross-hatching inFIG. 19.

The right pulmonary artery 206 can also include a branch point 1976 thatdivides the right pulmonary artery 206 into at least two additionalarteries 1978 that are distal to the branch point 207 defining the leftpulmonary artery 208 and the right pulmonary artery 206. As illustratedin FIG. 19, the plurality of electrodes 1944 can be positioned betweenthe branch point 207 defining the left pulmonary artery 208 and theright pulmonary artery 206 and the branch point 1976 that divides theright pulmonary artery 206 into at least two additional arteries 1978.In other words, the plurality of electrodes 1944 of the catheter 1930could be positioned so as to contact the posterior 221 and/or superiorsurface 223 of the right pulmonary artery 206 up to an including thebranch point 1976.

Once positioned in a pulmonary artery of the heart of the patient (e.g.,the right pulmonary artery 206 as illustrated in FIG. 19, the leftpulmonary artery 208, and/or the pulmonary trunk 202), one or moretherapeutic and/or calibrating electrical pulses can be deliveredthrough the plurality of electrodes 1944 of the catheter 1930. One ormore heart activity properties in response to the one or more electricalpulses are sensed from at least the first sensor 1966 positioned at afirst location within the vasculature of the heart 200.

The catheter 1830, 1930 may be permanently or reversibly implantableinto the vasculature. For example, the catheter 1830, 1930 may beretracted from the vasculature (e.g., after removing the anchor 1848,1948) after a duration. The duration may be determined based at leastpartially on a set duration (e.g., a certain number of hours or days(e.g., 12 hours, 18 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 6days, etc.)). The duration may be determined based at least partially ona response of a patient (e.g., retracted when the patient has improvedin an aspect by a certain amount or is deemed ready to have the catheter1830, 1930 removed).

FIG. 20 illustrates an example catheter 2030 and a separate first sensor2066 useful for the methods of the present disclosure. Similar to thecatheter 1830, the catheter 2030 includes an elongate catheter body 2032having a proximal or first end 2034 and a distal or second end 2036, aperipheral surface 2038 and an interior surface 2040 defining a lumen2042 (shown with a broken line) that extends between the first end 2034and the second end 2036 of the elongate catheter body 2032. The catheter2030 further includes a plurality of electrodes 2044 positioned alongthe peripheral surface 2038 of the elongate catheter body 2032, andconductive elements 2046 extending through the elongate body 2032between the plurality of electrodes 2044 and the first end 2034, asdiscussed herein. The catheter 2030 further includes an anchor 2048comprising struts 2050 that provide a peripheral surface 2052 that canengage vascular tissue (e.g., the lumen of either the right pulmonaryartery or the left pulmonary artery).

The catheter 2030 further includes a portion 2054 of the elongatecatheter body 2032, for example including the plurality of electrodes2044, where the portion 2054 can curve in a predefined radial directionwhen placed under longitudinal compression, as discussed herein. Theelongate catheter body 2032 of the catheter 2030 can also oralternatively include a lumen 2042 that can receive a shaping wire, asdiscussed herein.

In contrast to the catheter illustrated in FIGS. 18A through 18D,however, the catheter 2030 does not include a first sensor. Rather, asecond catheter 2080 includes a first sensor 2066. As illustrated inFIG. 20, the second catheter 2080 includes an elongate catheter body2082 having a first end 2084 and a second end 2086, a peripheral surface2088 and an interior surface 2090 defining a lumen 2092 (shown with abroken line) that extends between the first end 2084 and the second end2086 of the elongate catheter body 2082, where the lumen 2092 canreceive a guide wire for help in positioning the second catheter 2080 inthe vasculature of the heart. The second catheter 2080 further includesa first sensor 2066, as discussed herein, on the elongate catheter body2082 and a sensor conductor 2068 that extends through the elongatecatheter body 2082 to terminate at a connector port that can be used,for example, to releasably couple the first sensor 2066 to thestimulation system, as discussed herein.

As the first sensor 2066 is included on the second catheter 2080, thefirst sensor 2066 can be positioned in a location within the vasculatureof the patient that is different than the first location in which thecatheter 2030 is positioned. For example, the catheter 2030 can bepositioned with the plurality of electrodes 2044 positioned in the rightpulmonary artery, as discussed herein, while the first sensor 2066 ispositioned in the left pulmonary artery. In this way, one or moreelectrical pulses can be delivered through the catheter 2030 positionedin the right pulmonary artery of the heart that does not contain thefirst sensor 2066. In some examples, when the catheter 2030 ispositioned with the plurality of electrodes 2044 positioned in the leftpulmonary artery, the first sensor 2066 can be positioned in the rightpulmonary artery. In this way, one or more electrical pulses can bedelivered through the catheter 2030 positioned in the left pulmonaryartery of the heart that does not contain the first sensor 2066.

In some examples, the catheter 2030 can be positioned with the pluralityof electrodes 2044 positioned in either one of the left pulmonary arteryor the right pulmonary artery, and the first sensor 2066 on the secondcatheter 2080 can be positioned in the right ventricle of the heart. Thefirst sensor 2066 on the second catheter 2080 can also be positioned inthe right atrium of the heart.

In some examples, the first sensor 2066 on the second catheter 2080 canalso be positioned on the septal wall of the right atrium or theventricular septal wall of the heart. The elongate catheter body 2082 ofthe second catheter 2080 can include a positive fixation structure(e.g., a helical screw) that helps to secure the elongate catheter body2082 and the first sensor 2066 to the septal wall of the right atrium ofthe heart.

In some examples the first sensor 2066 on the second catheter 2080 canbe positioned in a superior vena cava of the heart. In some examples,the first sensor 2066 on the second catheter 2080 can be positioned inan inferior vena cava of the heart. In some examples, the first sensor2066 on the second catheter 2080 can be positioned in a coronary sinusof the heart. In a preferred example, when the first sensor 2066 ispositioned in the coronary sinus of the heart, the first sensor 2066 isused to sense at least one of a temperature and a blood oxygen level.

One or more cardiac properties can also or alternatively be sensed froma skin surface of the patient. An example of such a cardiac propertyincludes an electrocardiogram property, where the electrical activity ofthe heart can be sensed using electrodes, as are known, attached to thesurface of the patient's skin. Another example of such a cardiacproperty can include a Doppler echocardiogram, which can be used todetermine the speed and direction of the blood flow. Acoustic signalssensed from the skin surface of the patient may also be used as thecardiac property. The properties of the one or more electrical pulsesdelivered through the catheter positioned in the pulmonary artery of theheart can then be adjusted, as discussed herein, in response to the oneor more heart activity properties measured intravascularly and/or theone or more cardiac properties from the skin surface of the patient.

In some examples, a second sensor located at a second location withinthe vasculature of the heart can be used, in addition to the firstsensor, to sense one or more heart activity properties, as discussedherein, for example in response to the one or more electrical pulses.The second location is different than the first location. For example,the first location may be the left pulmonary artery and the secondlocation may be the right pulmonary artery; the first location may bethe left pulmonary artery and the second location may be the pulmonarytrunk; the first location may be the left pulmonary artery and thesecond location may be the right ventricle; the first location may bethe left pulmonary artery and the second location may be the rightatrium; the first location may be the left pulmonary artery and thesecond location may be the septal wall of the right atrium; the firstlocation may be the left pulmonary artery and the second location may bethe ventricular septal wall; the first location may be the leftpulmonary artery and the second location may be the superior vena cava;the first location may be the left pulmonary artery and the secondlocation may be the inferior vena cava; the first location may be theleft pulmonary artery and the second location may be the coronary sinus;and other permutations of these locations.

In some examples, the second sensor is the sensor 2066 of the secondcatheter 2080, and the first sensor is the sensor 266 of the catheter230. In some examples the first sensor and the second sensor can belocated on the same catheter (e.g., the catheter 230, the catheter2080). For example, both the first sensor and the second sensor can belocated on the second catheter 2080 for sensing at least two differentheart activity properties. For another example, both the first sensorand the second sensor can be located on the catheter 230 for sensing atleast two different heart activity properties. The properties of the oneor more electrical pulses delivered through the catheter positioned inthe pulmonary artery of the heart can be adjusted, as discussed herein,in response to the one or more heart activity properties received fromthe first sensor and the second sensor.

Neuromodulation of the heart according to the present disclosure can beaccomplished by applying electrical pulses in and/or around the regionof the pulmonary artery. For example, the neuromodulation of the presentdisclosure can apply the electrical pulses to the posterior, superiorwall, and/or the inferior wall of the right pulmonary artery.Preferably, neuromodulation of the present disclosure includes applyingthe electrical pulses to the posterior and/or superior wall of the rightpulmonary artery, although other positions in the right pulmonaryartery, the left pulmonary artery, and the pulmonary trunk are alsopossible. The electrical pulses are thereby applied to the autonomiccardiopulmonary nerves surrounding the right pulmonary artery. Theseautonomic cardiopulmonary nerves can include the right autonomiccardiopulmonary nerves and the left autonomic cardiopulmonary nerves.The right autonomic cardiopulmonary nerves include the right dorsalmedial cardiopulmonary nerve and the right dorsal lateralcardiopulmonary nerve. The left autonomic cardiopulmonary nerves includethe left ventral cardiopulmonary nerve, the left dorsal medialcardiopulmonary nerve, the left dorsal lateral cardiopulmonary nerve,and the left stellate cardiopulmonary nerve. Stimulation of other nervesproximate to the right pulmonary artery is also possible.

With reference to FIG. 19, one or more of the plurality of electrodes1944 of the catheter 1930 can be contacting the posterior surface 221 ofthe right pulmonary artery 206. From this location, the electricalpulses delivered through one or more of the plurality of electrodes 1944may be better able to treat and/or provide therapy (including adjuvanttherapy) to the patient experiencing a variety of cardiovascular medicalconditions, such as acute heart failure. The electrical pulses canelicit responses from the autonomic nervous system that may help tomodulate a patient's cardiac contractility. The electrical pulsesapplied by the methods described herein preferably affect heartcontractility more than the heart rate, which can help to improvehemodynamic control while possibly and/or reducing or minimizingunwanted systemic effects.

In accordance with several examples, a stimulation system iselectrically coupled to the plurality of electrodes of the cathetersdescribed herein (e.g., via the conductive elements extending throughthe catheter). The stimulation system can be used to deliver thestimulation energy (e.g., electrical current or electrical pulses) tothe autonomic cardiopulmonary fibers surrounding a pulmonary artery(e.g., the right or left pulmonary artery or the main pulmonary arteryor trunk). The stimulation system is used to operate and supply thestimulation energy (e.g., electrical current or electrical pulses) tothe plurality of electrodes of the catheter. The stimulation systemcontrols the various properties of the stimulation energy (e.g.,electrical current or electrical pulses) delivered across the pluralityof electrodes. Such properties include control of polarity (e.g., usedas a cathode or an anode), pulsing mode (e.g., unipolar, bi-polar,biphasic, and/or multi-polar), a pulse width, an amplitude, a frequency,a phase, a voltage, a current, a duration, an inter-pulse interval, adwell time, a sequence, a wavelength, and/or a waveform associated withthe stimulation energy (e.g., electrical current or electrical pulses).The stimulation system may operate and supply the stimulation energy(e.g., electrical current or electrical pulses) to differentcombinations and numbers of the one or more electrodes, including one ormore reference electrodes. The stimulation system can be external to thepatient's body or internal to the patient's body. When located outsidethe body, a professional can program the stimulation system and monitorits performance. When located within the patient, the housing of thestimulation system or an electrode incorporated in the housing can beused as a reference electrode for both sensing and unipolar pulsingmode.

Examples of non-electrical heart activity properties include, but arenot limited to, a pressure property, an acceleration property, anacoustic property, a temperature, or a blood chemistry property. Thenon-electrical heart activity properties may be sensed by at least afirst sensor positioned at a first location within the vasculature ofthe heart. In response to the one or more non-electrical heart activityproperties, a property of the one or more electrical pulses deliveredthrough the catheter positioned in the pulmonary artery of the heart canbe adjusted. Examples of such adjustments include, but are not limitedto, changing which electrode or electrodes of the plurality ofelectrodes on the catheter is/are used to deliver one or more electricalpulses. Adjustments can also be made to the properties of the electricalpulses, for example by changing at least one of an electrode polarity, apulsing mode, a pulse width, an amplitude, a frequency, a phase, avoltage, a current, a duration, an inter-pulse interval, a duty cycle, adwell time, a sequence, a wavelength, a waveform, and/or an electrodecombination of the one or more electrical pulses. It is possible toadjust combinations of electrodes used and the properties of theelectrical pulses provided by the electrodes. Adjusting a property ofthe one or more electrical pulses can include moving the catheter toreposition electrodes of the catheter in the pulmonary artery of theheart. Combinations of these adjustments are also possible.

By way of example, the stimulation energy (e.g., electrical current orelectrical pulses) can have a voltage between about 0.1 microvolts (mV)and about 75 volts (V) (e.g., about 0.1 mV, about 0.5 mV, about 1 mV,about 10 mV, about 100 mV or about 0.1 V, about 1 V, about 10 V, about20 V, about 30 V, about 40 V, about 50 V, about 60 V, about 75 V,between 1 V and 50 V, between 0.1 V and 10 V, ranges between suchvalues, etc.). The stimulation energy (e.g., electrical current orelectrical pulses) can also have an amplitude between about 1 milliamps(mA) to about 40 mA (e.g., about 1 mA, about 2 mA, about 3 mA, about 4mA, about 5 mA, about 10 mA, about 15 mA, about 20 mA, about 25 mA,about 30 mA, about 35 mA, about 40 mA, ranges between such values,etc.). The stimulation energy (e.g., electrical current or electricalpulses) can be delivered at a frequency of between 1 Hertz (Hz) andabout 100,000 Hz or 100 kilohertz (kHz) (e.g., between 1 Hz and 10 kHz,between 2 Hz and 200 Hz, about 1 Hz, about 2 Hz, about 10 Hz, about 25Hz, about 50 Hz, about 75 Hz, about 100 Hz, about 150 Hz, about 200 Hz,about 250 Hz, about 500 Hz, about 1,000 Hz or 1 kHz, about 10 kHz,ranges between such values, etc.). The electrical pulses can have apulse width between about 100 microseconds (μs) and about 100milliseconds (ms) (e.g., about 100 μs, about 200 μs, about 500 μs, about1,000 μs or 1 ms, about 10 ms, about 50 ms, about 100 ms, ranges betweensuch values, etc.). For variation of duty cycle, or the duration thatthe electrical pulses are delivered versus the duration that electricalpulses are not delivered, the electrical pulses may be delivered forbetween about 250 ms and about 1 second (e.g., about 250 ms, about 300ms, about 350 ms, about 400 ms, about 450 ms, about 500 ms, about 550ms, about 600 ms, about 650 ms, about 700 ms, about 750 ms, about 800ms, about 850 ms, about 900 ms, about 950 ms, ranges between suchvalues, etc.), and thereafter not delivered for between about 1 secondand about 10 minutes (e.g., about 1 second, about 5 seconds, about 10seconds, about 15 seconds, about 30 seconds, about 45 seconds, about 1minute, about 2 minutes, about 3 minutes, about 5 minutes, about 10minutes, ranges between such values, etc.). An optimized duty cycle may,for example, reduce response time, increase battery life, patientcomfort (reduce pain, cough, etc.), etc. The stimulation energy (e.g.,electrical current or electrical pulses) can also have a variety ofwaveforms, such as: square wave, biphasic square wave, sine wave,arbitrary defined waveforms that are electrically safe, efficacious, andfeasible, and combinations thereof. The stimulation energy (e.g.,electrical current or electrical pulses) may be applied to multipletarget sites via multiple electrodes at least partially simultaneouslyand/or sequentially.

In some examples, the waveform of a stimulation signal is a chargebalanced, constant current cathodic first biphasic waveform with a lowimpedance closed switch second phase electrode discharge. Pulse traincharacteristics can include, for example, a pulse amplitude betweenabout 8 mA and about 20 mA, a pulse width between about 2 ms and about 8ms, and a pulse frequency of about 20 Hz. Pulse amplitude and/or pulsewidth may be lower based on certain electrode designs.

The methods of the present disclosure can include assigning a hierarchyof electrode configurations from which to deliver the one or moreelectrical pulses. The hierarchy can include two or more predeterminedpatterns and/or combinations of the plurality of electrodes to use indelivering the one or more electrical pulses. For example, the one ormore electrical pulses can be delivered using the hierarchy of electrodeconfigurations. A heart activity property sensed in response to the oneor more electrical pulses delivered using the hierarchy of electrodeconfigurations can be analyzed. Such an analysis can include, forexample, determining which of the hierarchy of electrode configurationsprovide the highest contractility or relative contractility of thepatient's heart. Based on this analysis, an electrode configuration canbe selected to use for delivering the one or more electrical pulsesthrough the catheter positioned in the pulmonary artery of the patient'sheart.

In some examples, a method can include assigning a hierarchy to one ormore properties of the one or more electrical pulses delivered throughthe catheter positioned in the pulmonary artery of the heart. Thehierarchy can include providing an order of which property (e.g.,electrode polarity, pulsing mode, pulse width, amplitude, frequency,phase, voltage, current, duration, inter-pulse interval, duty cycle,dwell time, sequence, wavelength, or waveform of the one or moreelectrical pulses) is to be changed and by how much, and for apredetermined number of electrical pulses delivered to the patient'sheart. The predetermined number of electrical pulses can be, forexample, 10 to 100 electrical pulses at a given property of thehierarchy. The one or more heart activity properties can be recorded forthe predetermined number of the one or more electrical pulses deliveredto the patient's heart for a given property of the one or moreelectrical pulses. The one or more heart activity properties sensed inresponse to the one or more electrical pulses can then be analyzed. Forexample, the recorded properties for each set of predetermined numbersof pulses can be analyzed against other sets of recorded propertiesand/or against predetermined standards for a given heart activityproperties and/or cardiac property (e.g., contractility). Based on thisanalysis, an electrode configuration can be selected to use fordelivering the one or more electrical pulses through the catheterpositioned in the pulmonary artery of the patient's heart. As anon-limiting example, a current of 1 mA can be applied to an electrodefor 50 electrical pulses, followed by the application of a current of 10mA to the electrode for 50 electrical pulses. The responses at 1 mA and10 mA can be compared. If 10 mA works better, a current of 20 mA can beapplied to the electrode for 50 electrical pulses, and the responses at10 mA and 20 mA can be compared. If 10 mA works better, 10 mA may beselected as the current for the method. A wide variety of selectionprocesses may be used, including but not limited to iterative methods(e.g., comprising making comparisons until a limit is found at which adifference is negligible) and brute force methods (e.g., measuringresponses and selecting one magnitude after completion of all responsesor until a certain value is achieved). This can be repeated for one ormore additional properties according to the hierarchy (e.g., currentfollowed by frequency). The selection process may be the same ordifferent for each member of the hierarchy.

In some examples, a first electrical signal of a series of electricalsignals is delivered (e.g., via a stimulation system such as thestimulation system 2101) to an electrode in the pulmonary artery (e.g.,the right pulmonary artery, the left pulmonary artery, the pulmonarytrunk). After delivering the first electrical signal, a secondelectrical signal of the series of electrical signals is delivered(e.g., via the stimulation system) to the electrode. The secondelectrical signal differs from the first electrical signal by amagnitude of a first parameter of a plurality of parameters. Forexample, if the first parameter is current, the first electrical signalmay have a voltage such as 1 mA and the second electrical signal mayhave a different voltage such as 2 mA, while each of the otherparameters (e.g., polarity, pulse width, amplitude, frequency, voltage,duration, inter-pulse interval, dwell time, sequence, wavelength,waveform, and/or an electrode combination) are the same.

Sensor data indicative of one or more non-electrical heart activityproperties may be determined in response to delivering the series ofelectrical signals (e.g., via a sensor in the vasculature (e.g., as partof a same catheter that comprises the electrode, as part of a differentcatheter), via a sensor on a skin surface, combinations thereof, and thelike)). Electrical parameters to use for therapeutic modulation may beselected based at least partially on the sensor data. For example, theselected electrical parameters may comprise a selected magnitude of thefirst parameter. A therapeutic neuromodulation signal may be deliveredto the pulmonary artery using selected electrical parameters. Thetherapeutic neuromodulation signal may increase heart contractility(e.g., more than heart rate).

In some examples, a first series of electrical signals is delivered(e.g., via a stimulation system such as the stimulation system 501) toan electrode in the pulmonary artery (e.g., the right pulmonary artery,the left pulmonary artery, the pulmonary trunk). The first seriescomprises a first plurality of electrical signals. Each of the firstplurality of electrical signals comprises a plurality of parameters(e.g., polarity, pulsing mode, pulse width, amplitude, frequency, phase,voltage, current, duration, inter-pulse interval, duty cycle, dwelltime, sequence, wavelength, waveform, electrode combination, subsetsthereof, or the like). Each of the first plurality of electrical signalsof the first series only differs from one another by a magnitude of afirst parameter of the plurality of parameters (e.g., one of polarity,pulsing mode, pulse width, amplitude, frequency, phase, voltage,current, duration, inter-pulse interval, duty cycle, dwell time,sequence, wavelength, and waveform changes in each of the firstplurality of electrical signals). For example, if the first parameter iscurrent, the first plurality of electrical signals of the first seriesmay differ by having different currents such as 1 mA, 2 mA, 3 mA, 4 mA,etc., while each of the other parameters (e.g., polarity, pulsing mode,pulse width, amplitude, frequency, phase, voltage, duration, inter-pulseinterval, duty cycle, dwell time, sequence, wavelength, and waveform)are the same.

After the first series of electrical signals is delivered to theelectrode, a second series of electrical signals can be delivered (e.g.,via the stimulation system) to the electrode. The second seriescomprises a second plurality of electrical signals. Each of the secondplurality of electrical signals comprises the plurality of parameters.Each of the second plurality of electrical signals of the second seriesonly differs from one another by a magnitude of a second parameter ofthe plurality of parameters different than the first parameter (e.g., adifferent one of polarity, pulsing mode, pulse width, amplitude,frequency, phase, voltage, current, duration, inter-pulse interval, dutycycle, dwell time, sequence, wavelength, and waveform changes in each ofthe second plurality of electrical signals). For example, if the firstparameter is current, the second parameter may be related to timing suchas frequency or duty cycle. For example, in the case of frequency, thesecond plurality of electrical signals of the second series may differby having different frequencies such as 1 Hz, 2 Hz, 3 Hz, 4 Hz, etc.,while each of the other parameters (e.g., current, polarity, pulsingmode, pulse width, amplitude, phase, voltage, duration, inter-pulseinterval, duty cycle, dwell time, sequence, wavelength, and waveform)are the same.

Sensor data indicative of one or more non-electrical heart activityproperties may be determined in response to delivering the first seriesof electrical signals and the second series of electrical signals (e.g.,via a sensor in the vasculature (e.g., as part of a same catheter thatcomprises the electrode, as part of a different catheter), via a sensoron a skin surface, combinations thereof, and the like)). Electricalparameters to use for therapeutic modulation may be selected based atleast partially on the sensor data. For example, the selected electricalparameters may comprise a selected magnitude of the first parameter anda selected magnitude of the second parameter. A therapeuticneuromodulation signal may be delivered to the pulmonary artery usingselected electrical parameters. The therapeutic neuromodulation signalmay increase heart contractility (e.g., more than heart rate).

Other series of electrical signals may be delivered to the electrode,for example only differing from one another by a magnitude of adifferent parameter of the plurality of parameters than the firstparameter and the second parameter. As many parameters as may be desiredto have a selected value may be calibrated or optimized. An order of theparameters may be based on a hierarchy (e.g., first select a current,then select a frequency, etc.).

A calibration or optimization process may be performed once (e.g., whena catheter 1830, 1930 is initially positioned) or a plurality of times.For example, the process may be repeated periodically or after a certainduration (e.g., once per hour, per 2 hours, per 4 hours, per 6 hours,per 8 hours, per 12 hours, per 180 hours, per 24 hours, per 36 hours,per 2 days, per 60 hours, per 3 hours, etc.). In some implementationsthe process may be repeated upon detection of a change (e.g., by thesensor 266, 366, 466). For example, if a heart activity property changesby more than a certain percentage in a certain duration (e.g., ±10%,±25%, ±50%, etc. in ≤1 minute, ≤2 minutes, ≤5 minutes, etc.), that maybe indicative that the catheter and/or sensor changed position or thatsomething else in the system or patient may have changed (e.g., patientcondition, physiological status, other therapy regiments, etc.).

For example, FIG. 21 illustrates an example of a stimulation system2101. U.S. Provisional Patent App. No. 62/001,729, filed May 22, 2014,is incorporated herein by reference in its entirety, and morespecifically the stimulation system 11600 disclosed in FIG. 11 and page41, line 5 to page 42, line 19 are incorporated herein by reference. Asshown in FIG. 21, the stimulation system 2101 includes an input/outputconnector 2103 that can releasably join the conductive elements of thecatheter, conductive elements of a second catheter, and/or sensors forsensing the one or more cardiac properties from the skin surface of thepatient, as discussed herein. An input from the sensor can also bereleasably coupled to the input/output connector 11602 so as to receivethe sensor signal(s) discussed herein. The conductive elements and/orsensors may be permanently coupled to the stimulation system (e.g., notreleasably coupled).

The input/output connector 2103 is connected to an analog to digitalconverter 2105. The output of the analog to digital converter 2105 isconnected to a microprocessor 2107 through a peripheral bus 2109including, for example, address, data, and control lines. Themicroprocessor 2107 can process the sensor data, when present, indifferent ways depending on the type of sensor in use. Themicroprocessor 2107 can also control, as discussed herein, the pulsecontrol output generator 2111 that delivers the stimulation electricalenergy (e.g., electrical pulses) to the one or more electrodes via theinput/output connector 2103 and/or housing 2123.

The parameters of the stimulation electrical energy (e.g., properties ofthe electrical pulses) can be controlled and adjusted, if desired, byinstructions programmed in a memory 2113 and executed by a programmablepulse generator 2115. The memory 2113 may comprise a non-transitorycomputer-readable medium. The memory 2113 may include one or more memorydevices capable of storing data and allowing any storage location to bedirectly accessed by the microprocessor 2107, such as random accessmemory (RAM), flash memory (e.g., non-volatile flash memory), and thelike. The stimulation system 2101 may comprise a storage device, such asone or more hard disk drives or redundant arrays of independent disks(RAID), for storing an operating system and other related software, andfor storing application software programs, which may be the memory 2113or a different memory. The instructions in memory 2113 for theprogrammable pulse generator 2115 can be set and/or modified based oninput from the sensors and the analysis of the one or more heartactivity properties via the microprocessor 2107. The instructions inmemory 2113 for the programmable pulse generator 2115 can also be setand/or modified through inputs from a professional via an input 2117connected through the peripheral bus 2109. Examples of such an inputinclude a keyboard and/or a mouse (e.g., in conjunction with a displayscreen), a touch screen, etc. A wide variety of input/output (I/O)devices may be used with the stimulation system 2101. Input devicesinclude, for example, keyboards, mice, trackpads, trackballs,microphones, and drawing tablets. Output devices include, for example,video displays, speakers, and printers. The I/O devices may becontrolled by an I/O controller. The I/O controller may control one ormore I/O devices. An I/O device may provide storage and/or aninstallation medium for the stimulation system 2101. The stimulationsystem 2101 may provide USB connections to receive handheld USB storagedevices. The stimulation system 2101 optionally includes acommunications port 2119 that connects to the peripheral bus 2109, wheredata and/or programming instructions can be received by themicroprocessor 2107 and/or the memory 2113.

Input from the input 2117 (e.g., from a professional), thecommunications port 2119, and/or from the one or more heart activityproperties via the microprocessor 2107 can be used to change (e.g.,adjust) the parameters of the stimulation electrical energy (e.g.,properties of the electrical pulses). The stimulation system 2101optionally includes a power source 2121. The power source 2121 can be abattery or a power source supplied from an external power supply (e.g.,an AC/DC power converter coupled to an AC source). The stimulationsystem 2101 optionally includes a housing 2123.

The microprocessor 2107 can execute one or more algorithms in order toprovide stimulation. The microprocessor 2107 can also be controlled by aprofessional via the input 2117 to initiate, terminate, and/or change(e.g., adjust) the properties of the electrical pulses. Themicroprocessor 2107 can execute one or more algorithms to conduct theanalysis of the one or more heart activity properties sensed in responseto the one or more electrical pulses delivered using the hierarchy ofelectrode configurations and/or the hierarchy of each property of theone or more electrical pulses, for example to help identify an electrodeconfiguration and/or the property of the one or more electrical pulsesdelivered to the patient's heart. Such analysis and adjustments can bemade using process control logic (e.g., fuzzy logic, negative feedback,etc.) so as to maintain control of the pulse control output generator2111.

In some examples, the stimulation is operated with closed loop feedbackcontrol. In some examples, input is received from a closed-loopedfeedback system via the microprocessor 2107. The closed loop feedbackcontrol can be used to help maintain one or more of a patient's cardiacparameters at or within a threshold value or range programmed intomemory 2113. For example, under closed loop feedback control measuredcardiac parameter value(s) can be compared and then it can be determinewhether or not the measured value(s) lies outside a threshold value or apre-determined range of values. If the measured cardiac parametervalue(s) do not fall outside of the threshold value or thepre-determined range of values, the closed loop feedback controlcontinues to monitor the cardiac parameter value(s) and repeats thecomparison on a regular interval. If, however, the cardiac parametervalue(s) from a sensor indicate that one or more cardiac parameters areoutside of the threshold value or the pre-determined range of values oneor more of the parameters of the stimulation electrical energy will beadjusted by the microprocessor 2107.

The stimulation system 2101 may comprise one or more additionalcomponents, for example a display device, a cache memory (e.g., incommunication with the microprocessor 2107), logic circuitry, signalfilters, a secondary or backside bus, local buses, local interconnectbuses, and the like. The stimulation system 2101 may support anysuitable installation device, such as a CD-ROM drive, a CD-R/RW drive, aDVD-ROM drive, tape drives of various formats, USB device, hard-drive,communication device to a connect to a server, or any other devicesuitable for installing software and programs. The stimulation system2101 may include a network interface to interface to a Local AreaNetwork (LAN), Wide Area Network (WAN), or the Internet through avariety of connections including, but not limited to, standard telephonelines, LAN or WAN links, broadband connections, wireless connections(e.g., Bluetooth, WiFi), combinations thereof, and the like. The networkinterface may comprise a built-in network adapter, network interfacecard, wireless network adapter, USB network adapter, modem, or any otherdevice suitable for interfacing the stimulation system 2101 to any typeof network capable of communication and performing the operationsdescribed herein. In some examples, the stimulation system 2101 maycomprise or be connected to multiple display devices, which may be ofthe same or different in type and/or form. As such, any of the I/Odevices and/or the I/O controller may comprise any type and/or form ofsuitable hardware, software, or combination of hardware and software tosupport, enable, or provide for the connection and use of multipledisplay devices by the stimulation system 2101. The stimulation systemcan interface with any workstation, desktop computer, laptop or notebookcomputer, server, handheld computer, mobile telephone, any othercomputer, or other form of computing or telecommunications device thatis capable of communication and that has sufficient processor power andmemory capacity to perform the operations described herein and/or tocommunication with the stimulation system 2101. The arrows shown in FIG.21 generally depict the flow of current and/or information, but currentand/or information may also flow in the opposite direction depending onthe hardware.

Analysis, determining, adjusting, and the like described herein may beclosed loop control or open loop control. For example, in closed loopcontrol, a stimulation system may analyze a heart activity property andadjust an electrical signal property without input from a user. Foranother example, in open loop control, a stimulation system may analyzea heart activity property and prompt action by a user to adjust anelectrical signal property, for example providing suggested adjustmentsor a number of adjustment options.

In some examples, a method of non-therapeutic calibration comprisespositioning an electrode in a pulmonary artery of a heart andpositioning a sensor in a right ventricle of the heart. The systemfurther comprises delivering, via a stimulation system, a first seriesof electrical signals to the electrode. The first series comprises afirst plurality of electrical signals. Each of the first plurality ofelectrical signals comprises a plurality of parameters. Each of thefirst plurality of electrical signals of the first series only differsfrom one another by a magnitude of a first parameter of the plurality ofparameters. The method further comprises, after delivering the firstseries of electrical signals to the electrode, delivering, via thestimulation system, a second series of electrical signals to theelectrode. The second series comprises a second plurality of electricalsignals. Each of the second plurality of electrical signals comprisesthe plurality of parameters. Each of the second plurality of electricalsignals of the second series only differs from one another by amagnitude of a second parameter of the plurality of parameters. Thesecond parameter is different than the first parameter. The methodfurther comprises determining, via the sensor, sensor data indicative ofone or more non-electrical heart activity properties in response todelivering the first series of electrical signals and the second seriesof electrical signals. The method further comprises determining atherapeutic neuromodulation signal to be delivered to the pulmonaryartery using selected electrical parameters. The selected electricalparameters comprise a selected magnitude of the first parameter and aselected magnitude of the second parameter. The selected magnitudes ofthe first and second parameters are based at least partially on thesensor data.

In some examples, a method of non-therapeutic calibration comprisesdelivering a first electrical signal of a series of electrical signalsto an electrode in a first anatomical location and, after delivering thefirst electrical signal, delivering a second electrical signal of theseries of electrical signals to the electrode. The second electricalsignal differs from the first electrical signal by a magnitude of afirst parameter of a plurality of parameters. The method furthercomprises sensing, via a sensor in a second anatomical locationdifferent than the first anatomical location, sensor data indicative ofone or more non-electrical heart activity properties in response to thedelivery of the series of electrical signals, and determining atherapeutic neuromodulation signal to be delivered to the firstanatomical location using selected electrical parameters. The selectedelectrical parameters comprise a selected magnitude of the firstparameter. The selected magnitude of the first parameter is based atleast partially on the sensor data.

In some examples, the stimulation system can be used to help identify apreferred location for the position of the one or more electrodes alongthe posterior, superior and/or inferior surfaces of the main pulmonaryartery, left pulmonary artery, and/or right pulmonary artery. To thisend, the one or more electrodes of the catheter or catheter system areintroduced into the patient and tests of various locations along theposterior, superior and/or inferior surfaces of the vasculature usingthe stimulation system are conducted so as to identify a preferredlocation for the electrodes. During such a test, the stimulation systemcan be used to initiate and adjust the parameters of the stimulationelectrical energy (e.g., electrical current or electrical pulses). Suchparameters include, but are not limited to, terminating, increasing,decreasing, or changing the rate or pattern of the stimulationelectrical energy (e.g., electrical current or electrical pulses). Thestimulation system can also deliver stimulation electrical energy (e.g.,electrical current or electrical pulses) that is episodic, continuous,phasic, in clusters, intermittent, upon demand by the patient or medicalpersonnel, or preprogrammed to respond to a signal, or portion of asignal, sensed from the patient.

An open-loop or closed-loop feedback mechanism may be used inconjunction with the present disclosure. For the open-loop feedbackmechanism, a professional can monitor cardiac parameters and changes tothe cardiac parameters of the patient. Based on the cardiac parametersthe professional can adjust the parameters of the electrical currentapplied to autonomic cardiopulmonary fibers. Non-limiting examples ofcardiac parameters monitored include arterial blood pressure, centralvenous pressure, capillary pressure, systolic pressure variation, bloodgases, cardiac output, systemic vascular resistance, pulmonary arterywedge pressure, gas composition of the patient's exhaled breath and/ormixed venous oxygen saturation. Cardiac parameters can be monitored byan electrocardiogram, invasive hemodynamics, an echocardiogram, or bloodpressure measurement or other devices known in the art to measurecardiac function. Other parameters such as body temperature andrespiratory rate can also be monitored and processed as part of thefeedback mechanism.

In a closed-loop feedback mechanism, the cardiac parameters of thepatient are received and processed by the stimulation system, where theparameters of the electrical current are adjusted based at least in parton the cardiac parameters. As discussed herein, a sensor is used todetect a cardiac parameter and generate a sensor signal. The sensorsignal is processed by a sensor signal processor, which provides acontrol signal to a signal generator. The signal generator, in turn, cangenerate a response to the control signal by activating or adjusting oneor more of the parameters of the electrical current applied by thecatheter to the patient. The control signal can initiate, terminate,increase, decrease or change the parameters of the electrical current.It is possible for the one or more electrodes of the catheter to be usedas a sensor a recording electrode. When necessary these sensing orrecording electrodes may deliver stimulation electrical energy (e.g.,electrical current or electrical pulses) as discussed herein.

The stimulation system can also monitor to determine if the one or moreelectrodes have dislodged from their position within the right pulmonaryartery. For example, impedance values can be used to determine whetherthe one or more electrodes have dislodged from their position within theright pulmonary artery. If changes in the impedance values indicate thatthe one or more electrodes have dislodged from their position within theright pulmonary artery, a warning signal is produced by the stimulationsystem and the electrical current is stopped.

In several examples, the catheters provided herein include a pluralityof electrodes, which includes two or more electrodes. It is understoodthat the phrase “a plurality of electrodes” can be replaced herein withtwo or more electrodes if desired. For the various examples of cathetersand systems disclosed herein, the electrodes can have a variety ofconfigurations and sizes. For example, the electrodes discussed hereincan be ring-electrodes that fully encircle the body on which they arelocated. The electrodes discussed herein can also be a partial ring,where the electrode only partially encircles the body on which they arelocated. For example, the electrodes can be partial ring electrodes thatpreferably only contact the luminal surface of the main pulmonary arteryand/or pulmonary arteries, as discussed herein. This configuration mayhelp to localize the stimulation electrical energy, as discussed herein,into the vascular and adjacent tissue structures (e.g., autonomicfibers) and away from the blood. The electrodes and conductive elementsprovided herein can be formed of a conductive biocompatible metal ormetal alloy. Examples of such conductive biocompatible metal or metalalloys include, but are not limited to, titanium, platinum or alloysthereof. Other biocompatible metal or metal alloys are known.

For the various examples, the elongate body of the catheters providedherein can be formed of a flexible polymeric material. Examples of suchflexible polymeric material include, but are not limited to, medicalgrade polyurethanes, such as polyester-based polyurethanes,polyether-based polyurethanes, and polycarbonate-based polyurethanes;polyamides, polyamide block copolymers, polyolefins such as polyethylene(e.g., high density polyethylene); and polyimides, among others.

Each of the catheters and/or catheter systems discussed herein canfurther include one or more reference electrodes positioned proximal tothe one or more electrodes present on the elongate body. These one ormore reference electrodes can each include insulated conductive leadsthat extend from the catheter and/or catheter system so as to allow theone or more reference electrodes to be used as common or returnelectrodes for electrical current that is delivered through one or moreof the one or more electrodes on the elongate body of the catheterand/or catheter system.

With respect to treating cardiovascular medical conditions, such medicalconditions can involve medical conditions related to the components ofthe cardiovascular system such as, for example, the heart and aorta.Non-limiting examples of cardiovascular conditions includepost-infarction rehabilitation, shock (hypovolemic, septic, neurogenic),valvular disease, heart failure including acute heart failure, angina,microvascular ischemia, myocardial contractility disorder,cardiomyopathy, hypertension including pulmonary hypertension andsystemic hypertension, orthopnea, dyspenea, orthostatic hypotension,dysautonomia, syncope, vasovagal reflex, carotid sinus hypersensitivity,pericardial effusion, and cardiac structural abnormalities such asseptal defects and wall aneurysms.

In some examples, a catheter, for example as discussed herein, can beused in conjunction with a pulmonary artery catheter, such as aSwan-Ganz type pulmonary artery catheter, to deliver transvascularneuromodulation via the pulmonary artery to an autonomic target site totreat a cardiovascular condition. In certain such examples, the catheter(or catheters) is housed within one of the multiple lumens of apulmonary artery catheter.

In addition to the catheter and catheter system of the presentdisclosure, one or more sensing electrodes can be located on or withinthe patent. Among other things, the sensing electrodes can be used todetect signals indicting changes in various cardiac parameters, wherethese changes can be the result of the pulse of stimulation electricalenergy delivered to stimulate the nerve fibers (e.g., autonomic nervefibers) surrounding the main pulmonary artery and/or one or both of thepulmonary arteries. Such parameters include, but are not limited to, thepatient's heart rate (e.g., pulse), among other parameters. The sensingelectrodes can also provide signals indicting changes in one or moreelectrical parameter of vasculature (electrical activity of the cardiaccycle). Such signals can be collected and displayed, as are known, usingknown devices (e.g., electrocardiography (ECG) monitor) or a stimulationsystem, as discussed herein, which receives the detected signals andprovides information about the patient.

Other sensors can also be used with the patient to detect and measure avariety of other signals indicting changes in various cardiacparameters. Such parameters can include, but are not limited to, bloodpressure, blood oxygen level and/or gas composition of the patient'sexhaled breath. For example, catheter and catheter system of the presentdisclosure can further include a pressure sensor positioned within orin-line with the inflation lumen for the inflatable balloon. Signalsfrom the pressure sensor can be used to both detect and measure theblood pressure of the patient. Alternatively, the catheter and cathetersystem of the present disclosure can include an integrated circuit forsensing and measuring blood pressure and/or a blood oxygen level. Suchan integrated circuit can be implemented using 0.18 μm CMOS technology.The oxygen sensor can be measured with optical or electrochemicaltechniques as are known. Examples of such oxygen sensors includereflectance or transmissive pulse oximetry those that use changes inabsorbance in measured wavelengths optical sensor to help determined ablood oxygen level. For these various examples, the elongate body of thecatheter can include the sensor (e.g., a blood oxygen sensor and/or apressure sensor) and a conductive element, or elements, extendingthrough each of the elongate body, where the conductive element conductselectrical signals from the blood oxygen sensor and/or the pressuresensor.

The detected signals can also be used by the stimulation system toprovide stimulation electrical energy in response to the detectedsignals. For example, one or more of these signals can be used by thestimulation system to deliver the stimulation electrical energy to theone or more electrodes of the catheter or catheter system. So, forexample, detected signals from the patent's cardiac cycle (e.g., ECGwaves, wave segments, wave intervals or complexes of the ECG waves) canbe sensed using the sensing electrodes and/or timing parameter of thesubject's blood pressure. The stimulation system can receive thesedetected signals and based on the features of the signal(s) generate anddeliver the stimulation electrical energy to the one or more electrodeof the catheter or catheter system. As discussed herein, the stimulationelectrical energy is of sufficient current and potential along with asufficient duration to stimulate one or more of the nerve fiberssurrounding the main pulmonary artery and/or one or both of thepulmonary arteries so as to provide neuromodulation to the patient.

FIG. 22A is a perspective view of an example of a portion 2200 of acatheter. FIG. 22B is a side elevational view of the portion 2200 ofFIG. 22A. FIG. 22C is a distal end view of the portion 2200 of FIG. 22A.FIG. 22D is a proximal end view of the portion 2200 of FIG. 22A. Theportion 2200 may be coupled to or form part of a catheter (e.g., anall-in-one catheter or a telescoping catheter), for example as describedherein.

The portion 2200 comprises a first cut hypotube 2202 and a second cuthypotube 2204 coupled at points 2206. As may be appropriate for any ofthe cut hypotubes described herein, a sheet may be cut and rolled into ahypotube with an intermediate shape setting into a tube or directly intoa final shape. The first cut hypotube 2202 comprises a cylindrical(e.g., uncut) portion 2208 and a plurality of splines 2210. The secondcut hypotube 2204 comprises a cylindrical (e.g., uncut) portion 2212 anda plurality of splines 2214. As may be best seen in FIG. 22B, thesplines 2210 are convex and the splines 2214 are concave.

In the example illustrated in FIGS. 22A and 22B, the distal ends of thesplines 2210 are coupled radially inward of, but proximate to, thedistal ends of the splines 2214 at the points 2206. In some examples,the distal ends of the splines 2210 may be coupled to the splines 2214even further radially inward. In some examples, the distal ends of thesplines 2214 may be coupled radially inward of the distal ends of thesplines 2210. The points 2206 may be proximate to the distal ends of thesplines 2210 and the distal ends of the splines 2214 (e.g., as shown inFIGS. 22A and 22B), between the distal ends of the splines 2214 andpoints along the splines 2210 (e.g., an approximate longitudinalmidpoint, about 75% of the length closer to the distal end, etc.), orbetween the distal ends of the splines 2210 and points along the splines2214 (e.g., including examples in which the splines 2214 are configuredto be convex distal to the points 2206).

As shown in FIGS. 22C and 22D, the cylindrical portion 2212 telescopesradially inward of the cylindrical portion 2208. The cylindrical portion2212 has a lower diameter than the cylindrical portion 2208. As thecylindrical portion 2208 and the cylindrical portion 2212 moverelatively away from each other (e.g., by distal advancement of thesecond cut hypotube 2204 and/or proximal retraction of the first cuthypotube 2202), the splines 2204 push the splines 2210 radially outward.

FIGS. 22A-22D illustrate six splines 2210 and six splines 2214. Othernumbers of splines 2210, 2214 are also possible (e.g., between 2 and 12(e.g., about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, ranges between suchvalues, etc.)). The splines 2210, 2214 may be uniformlycircumferentially spaced, or some splines 2210, 2214 may be closercircumferentially. The splines 2210, 2214 may provide a circumferentialcoverage between about 60° and 360° (e.g., about 60°, about 90°, about120°, about 180°, about 210°, about 240°, about 270°, about 300°, 360°,ranges between such values, etc.). If the portion 2200 is rotatable tofind a target nerve, the circumferential coverage may optionally be atthe lower end of the range. As described with respect to FIG. 22E, atleast some of the splines 2210 may comprise electrodes. Others of thesplines 2210 may be free of electrodes or include electrodes that arenot used, but may act as apposition arms (e.g., in cases when thesplines 2210 are not pushed to a side of a vessel due to rigidity and anatural course of a navigation path), which can help push the electrodesagainst or close to the tissue.

FIGS. 22E-22G are side partial cross-sectional views of an example of acatheter 2220 including the portion 2200 of FIG. 22A. The splines 2210comprise electrodes 2222, for example on an exterior surface, annularlyaround, in U-shaped channels (e.g., as described herein), as part of amesh covering (e.g., as described with respect to FIG. 4C), etc. In someexamples, the length 2223 of the parts of the splines 2210 comprisingelectrodes is between about 20 mm and about 40 mm (e.g., about 20 mm,about 25 mm, about 30 mm, about 35 mm, about 40 mm, ranges between suchvalues, etc.). The first cut hypotube 2202 is coupled to a cannula orsheath 2226. The first cut hypotube 2202 may be coupled in a lumen ofthe cannula 2226 (e.g., as shown in FIGS. 22E and 22G), on an outside ofthe cannula 2226, end-to-end, by tethers, etc. The cannula 2226 may havea diameter between about 7 Fr and about 11 Fr (e.g., about 7 Fr, about 8Fr, about 9 Fr, about 10 Fr, about 11 Fr, ranges between such values,etc.). The second cut hypotube 2204 is coupled to an inner member 2224.The second cut hypotube 2204 may be coupled in a lumen of the innermember 2224 (e.g., as shown in FIG. 22G), on an outside of the innermember 2224, end-to-end, by tethers, etc. FIG. 22G shows the first cuthypotube 2202 in cross-section to show the coupling between the secondcut hypotube 2204 and the inner member 2224. Relative movement betweenthe inner member 2224 (and thus the second cut hypotube 2204) and thecannula 2226 (and thus the first cut hypotube 2202) can cause thesplines 2210 to flex radially (e.g., proximal retraction of the cannula2226 and/or distal advancement of the inner member 2224 can cause thesplines 2210 to flex radially outward, proximal retraction of the innermember 2210 and/or distal advancement of the cannula 2226 can cause thesplines 2210 to flex radially inward), as shown in FIG. 22F. Since thesplines 2214 can push the splines 2210 radially outward, the splines2210 can be free of a taper, which can reduce the profile and length ofthe catheter 2220 and the throw distance. In some examples, the diameter2225 of the splines 2210 in the expanded state is between about 15 mmand about 35 mm (e.g., about 15 mm, about 20 mm, about 25 mm, about 30mm, about 35 mm, ranges between such values, etc.).

A potential advantage of a catheter 2220 in which the splines 2210 arein a collapsed position (FIG. 22F) is that in the event of a failure(e.g., proximal breakage), the splines 2210 collapse inwardly instead ofexpanding. That is, the collapsed state is the default state, which maybe safer than an expanded state being a default state, for example whenthe catheter 2220 passes by valves, chordae tendinae, etc. A potentialadvantage of not using shape memory material, which is possible whenexpansion is due to longitudinal movement, is reduced costs.

In some examples, the splines 2210 may be self-expanding, for exampleable to expand upon removal of a force from the inner member 2224.Reduced length can be useful when a target vessel is short, for examplea pulmonary artery. Relative movement may be manual or, for example asdescribed herein, spring assisted.

In some examples, the catheter 2220 may comprise a fixation systemseparate from the portion 2200. For example, the fixation system mayextend through the lumen of the second cut hypotube 2204. The fixationsystem may be axially and rotationally movable relative to the portion2200, which can be useful to provide appropriate fixation and nervetargeting. Once a user is satisfied with the positions of the portion2200 and the fixation system, the portion 2200 and the fixation systemmay be coupled (e.g., at a handle outside the subject). Even oncecoupled, the portion 2200 and the fixation system may be able to rotate(e.g., ±20° and/or move longitudinally, (e.g., ±1 cm, ±2 cm) relative toeach other. The portion 2200 may be moved to improve nerve targetingeven while the fixation mechanism does not move, which can reduce tissuedisturbance. In some examples, distal ends of the splines 2214 mayprovide alternate or additional fixation.

In some examples, the splines 2210, the splines 2204, or another part ofthe portion 2200 or the catheter 2220 comprises a sensor (e.g., apressure sensor, a contractility sensor, etc.).

In some examples, rotation of a proximal handle may impart longitudinalmovement and/or rotational movement that is not 1:1 at the distal end ofthe catheter 2220, for example due to catheter shape, bending, or otherfactors.

FIGS. 22H-22L are side elevational and partial cross-sectional views ofexamples of catheter deployment systems 2230, 2240. In FIGS. 22H-22J,the proximal end or handle of the catheter deployment systems areillustrated. In FIGS. 22K and 22L, the proximal end or handle of thecatheter deployment systems are illustrated. The catheter deploymentsystems 2230, 2240 may be used, for example, with the catheter 2220.

The system 2230 comprises a spring 2232. The spring abuts a gripper2234, which is coupled to the inner member 2224. The spring 2232 has anegative spring constant (restoring force is inwards), but a springhaving a positive spring constant (restoring force outwards) is alsopossible by rearrangement of other features. To expand the splines 2210,a handle element 2236 such as a knob is pushed distally relative to thecannula 2226, against the force of the spring 2232. The system 2230 maycomprise a locking mechanism 2238 configured to hold the handle element2236 in a distal position. In the system 2230, in the event of a breakin the system 2230 (e.g., failure of the locking mechanism 2238), thespring 2232 retracts the inner element 2224, collapsing the splines2210, which can allow for easy recovery of the catheter 2220. The spring2232 may provide a range of deployment options compared to a solelymanual structure, for example due to forces provided by the spring 2232.

FIG. 22I shows an example of the locking mechanism 2238 comprising aplurality of arms that can resiliently hold the handle element 2236 in adistal position. The arms may be open at a proximal end, and the handleelement 2236 (e.g., the entire handle element 2236) may be captured inthe arms. When the splines 2210 are to be collapsed, the arms may beopened, allowing the spring 2232 to force the handle element 2236proximally, retracting the inner element 2224 and collapsing the splines2210.

FIG. 22J shows anotehr example of the locking mechanism 2238 comprisinga plurality of arms that can resiliently hold the handle element 2236 ina distal position. The arms may be closed at a proximal end. The armsmay be biased radially outward to promote radial expansion. The arms mayact as secondary leaf springs. In some examples, the handle element 2236and the closed proximal end of the locking mechanism 2238 compriseVelcro®, magnets, threads, or other features to hold the handle element2236 in a distal position. When the splines 2210 are to be collapsed,the handle element 2236 may be disengaged, allowing the spring 2232 (andthe arms) to force the handle element 2236 proximally, retracting theinner element 2224 and collapsing the splines 2210. In some examples,compressing the arms can cause the handle element 2236 to be disengaged.

The system 2240 comprises a spring 2242. The spring abuts a gripper2244, which is coupled to the inner member 2224. The spring 2242 has apositive spring constant (restoring force is inwards), but a springhaving a positive spring constant (restoring force outwards) is alsopossible by rearrangement of other features.

In FIG. 22K, to expand the splines 2210, a handle element coupled to theinner member 2224 is pulled proximally relative to the cannula 2226,against the force of the spring 2242. The pulling element 2246 iscoupled to the inner member 2224. The pulling element 2246 is coupled tosplines 2247 (e.g., similar to the splines 2214 but opposite inorientation such that the splines 2247 extend distally in a collapsedstate). As the pulling element 2246 is pulled proximally, the splines2247 expand radially outward, pushing the splines 2210 radially outwardto an expanded state.

In FIG. 22L, the splines 2210 have a slightly tapered shapes so that apulling element 2246 can rest between the splines 2210 in a collapsedstate and interact with the splines 2210 during retraction. To expandthe splines 2210, a handle element coupled to the inner member 2224 ispulled proximally relative to the cannula 2226, against the force of thespring 2242. The pulling element 2246 is coupled to the inner member2224. As the pulling element 2246 is pulled proximally, the proximal endof the pulling element 2246 bears against the inside surfaces of thesplines 2210, pushing the splines 2210 radially outward to an expandedstate.

In the system 2240 of FIGS. 22K and 22L, in the event of a break in thesystem 2240, the spring 2242 advances the inner element 2224, collapsingthe splines 2210, which can allow for easy recovery of the catheter2220. The spring 2242 may provide a range of deployment options comparedto a solely manual structure, for example due to forces provided by thespring 2242.

FIG. 22M illustrates an example part 2250 of the portion 2200 of FIG.22A. Rather than a first cut hypotube 2202, the part 2250 comprises ahypotube 2252 coupled to a plurality of wires 2254 shaped into splines2210. The orange wires 2254 o show the shapes of the splines 2210 in anopen or expanded state, and the grey wires 2254 g show the shapes of thesplines 2210 in a closed or collapsed state. As with the splines 2210 ofthe first cut hypotube 2202, the wires 2254 may comprise shape memorymaterial (e.g., nitinol) and/or may be moved to an expanded position bya second cut hypotube 2204 or similar device. Referring to FIGS. 22E and4C, the part 2250 may comprise electrodes on the wires 2254, on a meshattached to the wires 2254, combinations thereof, and the like.

FIG. 23A is a perspective view of an example segment 2300 of a strut.The segment 2300 generally has a U-shape. The segment 2300 compriseswalls 2302 at least partially defining a channel or trough 2304. Thewalls 2302 and trough 2304 may be formed in a variety of ways. In someexamples, a wire may be extruded in the U-shape. In some examples, ahypotube may be cut to form generally rectangular struts, and the trough204 may be formed by removing material from the struts (e.g., bymilling). In some examples, sides of a flat wire may be bent upwards. Insome examples, the U-shape may comprise plastic (e.g., extruded, molded,etc.). The trough 2304 may be lined with insulative material. In someexamples, the insulative material comprises epoxy. In some examples, atrough 2304 lined with insulative material can help to make electrodesdirectional, which can help to aim energy at a vessel wall and at anerve. A plurality of wires or leads or conductors 2306 may lie in thetrough 2304. Positioning the wires 2306 in the trough 2304 can aid inmanufacturing (positioning of the wires 2306), may reduce the risk thatthe conductors may cross-talk, and/or may protect the wires 2306 frombreaking. The wires 2306 are electrically connected to electrodes,transducers, and the like that can be used to provide neuromodulation.FIGS. 23B-23F show examples of configurations that may be used toposition wires 2306, insulator, and an electrode 2308 at least partiallyin a U-shaped segment of a strut. In some examples, a U-shaped segmentmay be coupled to a strut (e.g., adhered, welded, soldered, interferencefit, etc.).

The trough 2304 may have a depth 2370 between about 0.003 inches andabout 0.02 inches (e.g., about 0.003 inches, about 0.005 inches, about0.01 inches, about 0.015 inches, about 0.02 inches, ranges between suchvalues, and the like). The trough 2306 may have a width 2372 betweenabout 0.15 inches and about 0.1 inches (e.g., about 0.015 inches, about0.02 inches, about 0.025 inches, about 0.05 inches, about 0.06 inches,about 0.08 inches, about 0.1 inches, ranges between such values, and thelike).

FIG. 23B is a transverse cross-sectional view of an example of a strut2320. The strut 2320 includes walls 2302 at least partially defining atrough. In some examples, the walls 2302 form a depth 2370 configured toat least partially laterally cover an electrode 2308. A plurality ofwires 2306 lies in the trough. The wires 2306 are covered by aninsulating sheet or insert 2310. Each of the wires 2306 may be coatedwith insulative material and/or the insulating sheet 2310 may provideinsulation for the wires 2306. Insulation at welds and at junctionsbetween wires 2306 and electrodes 2308 can inhibit or prevent damagefrom body fluids and corrosion. An electrode 2308 is electricallyconnected to one of the wires 2306 through the insulating sheet 2310.The electrode 2308 illustrated in FIG. 23B has a rectangularcross-section. FIG. 23C illustrates a transverse cross-sectional view ofan example of a strut 2325 in which the electrode 2308 has a roundedcross-section (e.g., shaped as a dome), which can help to reduce edgeeffects and hot spots due to sharp edges. In some examples in which theelectrode 2308 includes sharp edges, insulating material can at leastpartially cover the sharp edges, which can help reduce edge effects. Theelectrode 2308 may be sunk in a well of insulative material such thatonly a top surface is exposed, which can help the electrode 2308 to bedirectional. The electrode 2308, as with all electrodes describedherein, may lack sharp edges and/or lack sharp edges that are notcovered with insulative material.

FIG. 23D is a cross-sectional view of another example of a strut 2330.The strut 2330 includes walls 2302 at least partially defining a trough.A plurality of wires 2306 lies in the trough. The wires 2306 are coveredby an insulating layer 2312. The insulating layer 2312 may comprise, forexample, silicone or any suitable insulating, flexible material. Each ofthe wires 2306 may be coated with insulative material and/or theinsulating layer 2312 may provide insulation for the wires 2306. Anelectrode 2308 is electrically connected to one of the wires 2306through the insulating layer 2312. The electrode 2308 may be the sameheight as the insulating layer 2312. The insulating layer 2312 mayinclude dome shapes.

FIG. 23E is a transverse cross-sectional view of yet another example ofa strut 2340. The strut 2340 includes walls 2302 at least partiallydefining a trough. A plurality of wires 2306 lies in the trough. Thewires 2306 are covered by an insulating layer 2314. The insulating layer2314 may comprise, for example, silicone or any suitable insulating,flexible material. Each of the wires 2306 may be coated with insulativematerial and/or the insulating layer 2314 may provide insulation for thewires 2306. An electrode 2308 is electrically connected to one of thewires 2306 through the insulating layer 2314. The electrode 2308 may bethe same height as the insulating layer 2314. The insulating layer 2312may include a generally flat or planar upper surface.

FIG. 23F is a transverse cross-sectional view of still another exampleof a strut 2350. The strut 2350 includes walls 2302 at least partiallydefining a trough. A plurality of wires 2306 lies in the trough. Thewires 2306 are covered by an insulating layer 2316. The insulating layer2316 may comprise, for example, silicone or any suitable insulating,flexible material. Each of the wires 2306 may be coated with insulativematerial and/or the insulating layer 2316 may provide insulation for thewires 2306. An electrode 2308 is electrically connected to one of thewires 2306 through the insulating layer 2316. The insulating layer 2316may include a generally crowned surface. The electrode 2308 may be thesunken into the insulating layer 2316, which can help to reduce edgeeffects. Reducing edge effects can increase uniformity of an electricfield emanating from the electrode 2308. An electrode 2308 that is belowan upper surface of the insulating layer 2316 may be spaced from tissue,which can allow blood flow across the electrode 2308.

The insulating layer 2312, 2314, 2316 may maintain positions of thewires 2306 in the U-shaped trough, for example inhibiting tanglingand/or maintaining a spatial separation. The insulating layer 2312,2314, 2316 may protect the wires 2306, for example from body fluids andexternal forces.

The insulating layer 2312, 2314, 2316 may be deposited over the wires2306 in the trough. The insulating layer 2312, 2314, 2316 may be curedand then ablated (e.g., laser ablated, milled) to allow the positioningof the electrode 2308 and a connector thereto. In some examples, a plug(e.g., comprising a material that doesn't stick to the material of theinsulating layer 2312, 2314, 2316, such as PTFE) may be positioned inthe insulating layer 2312, 2314, 2316 and then removed after curing toallow the positioning of the electrode 2308 and a connector thereto.

FIG. 23G is a top partial cross-sectional view of an example segment2360 of a strut. As illustrated, the wires 2306 are spatially separated.In examples in which the wires 2306 are not individually insulated, theinsulating material can inhibit or prevent electrical communicationbetween the wires 2306. A first wire 2306 a is connected to a firstelectrode 2308 a. A second wire 2306 b is connected to a secondelectrode 2308 b. A third wire 2306 c is connected to a third electrode(not shown).

FIG. 23H illustrates an example of a strut system 2380 comprising aplurality of struts or splines 2382 each having a generally U-shapedtrough. The U-shaped troughs can help to align or maintain the spacingor separation distance between the struts 2382. FIG. 23I shows anexample in which a distance b between a first strut 2382 a and a secondstrut 2382 b is less than a distance a between a third strut 2382 c andthe second strut 2382 b. FIG. 23J shows an example in which a distance2374 between a first strut 2382 a and a second strut 2382 b issubstantially the same as a distance a between a third strut 2382 c andthe second strut 2382 b. In some examples, the distance b or 2374between struts or strut-to-strut spacing may be between about 10 mm andabout 15 mm (e.g., about 10 mm, about 11 mm, about 12 mm, about 13 mm,about 14 mm, about 15 mm, ranges between such values, etc.). With theU-shape, the splines 2382 may flex less in a radial configuration than around-wire spline system, which can help to keep spacing between thesplines more consistent, whether the spacing is meant to be consistentor varying. The U-shape may reduce the likelihood that the splines 2382slide relative to each other and that the electrodes 2308 in each of thesplines 2382 slide relative to each other, which can maintain spacing ofthe electrodes.

FIG. 23K illustrates an example of an electrode on wire system 2390. Thesystem 2390 comprises a wire 2392 and an electrode 2394 over (e.g.,radially outward of, annularly or arcuately around) the wire 2392. Thewire 2392 may comprise a shape memory material (e.g., nitinol). Theelectrode 2394 may comprise, for example, a platinum-iridium electrode.Other materials for the wire 2392 and the electrode 2394 are alsopossible. The system 2390 may comprise an insulator 2396 between thewire 2392 and the electrode 2394. The electrode 2394 may be electricallycoupled to a conductor wire 2398. In some examples, a single wire 2392may comprise a plurality of electrodes 2394, for example forming anarray.

FIG. 23L is a cross-sectional view of an electrode 2308 spaced from avessel wall 2397. The blood vessel is spaced from a nerve 2399. Theelectrode 2308 may be positioned as close to the vessel wall 2397 aspossible so that the electrode 2308 is as close to the nerve 2399 aspossible. In some examples, the electrode 2308 may be intentionallyspaced from the vessel wall 2397 a distance d, which can allow blood toflow both under and over the electrode 2308, for example as shown by thethick arrows. In some examples, the distance d is between about 0.1 mmand about 1 mm (e.g., about 0.1 mm, about 0.2 mm, about 0.3 mm, about0.5 mm, about 0.7 mm, about 0.9 mm, about 1 mm, ranges between suchvalues, etc.). Referring again to FIG. 23F, the insulating material2316, for example, may act as a spacer. Allowing blood to flow over theelectrode 2308 may inhibit corrosion of the electrode 2308. Allowingblood to flow over the electrode 2308 may allow blood to contact thevessel wall 2397 in the area of the electrode 2308 such that cells maybe replenished. In some examples, the electrode may compriselongitudinal channels, a bumpy surface, etc. to allow blood to flowradially outward of the electrode 2308 but to still be closer to thenerve 2399. In certain such examples, surface area of the electrode 2308may be advantageously increased.

FIGS. 23Ni-23Nix illustrate an example method of manufacturingcomponents on a substrate 2301. The substrate 2301 may comprise, forexample, a shape-memory alloy such as nitinol forming a spline of anelectrode system. Flex-circuit processing can be used to patternelectrodes, conductors, insulators, and other components (e.g.,resistors) on a spline. In FIG. 23Ni, an insulating layer 2303comprising insulative material (e.g., oxide, polyimide) is depositedover the substrate 2301. If the substrate 2301 is insulating, the layer2303 may be omitted. As used with respect to FIG. 23Ni-23Nix, the term“over” could mean on or directly on as viewed from a certainorientation, and is not intended to limit intervening layers, and theterm “layer” could mean a plurality of layers (e.g., including adhesivelayers). In FIG. 23Nii, a conductive layer 2305 comprising conductivematerial (e.g., aluminum, copper, doped silicon) is deposited over theinsulating layer 2303. In FIG. 23Niii, the conductive layer 2305 ispatterned into conductor wires 2306 (e.g., using photolithography,lift-off lithography, etc.). In some examples, the conductor wires 2306may be formed directly (e.g., using screen printing, inkjet printing).In FIG. 23Niv, an insulating layer 2307 insulative material (e.g.,oxide, polyimide) is deposited over the conductor wires 2306 and theinsulating layer 2303. The insulative material of the insulating layers2303, 2307 may be the same or different. In FIG. 23Nv, a via 2311 isformed (e.g., via etching, milling) in the insulating layer 2307,exposing a portion of the middle conductor wire 2306. In FIG. 23Nvi, aconductive layer 2309 comprising conductive material (e.g., aluminum,copper, doped silicon) is formed over the insulating layer 2307 andfilling the via 2311. The conductive material of the conductive layers2305, 2309 may be the same or different. In FIG. 23Nvii, the conductivelayer 2309 is patterned into electrodes 2308. Wet etching, for example,may help to form a domed shape of the electrode 2308. Although notillustrated, vias 2311 may be formed to connect each conductor wire 2306to a different electrode 2308. In FIG. 23Nviii, an insulating layer 2313(e.g., comprising oxide, polyimide) is formed over the electrode 2308and the insulating layer 2307. The insulative material of the insulatinglayers 2303, 2307, 2313 may be the same or different. In FIG. 23Nix, theinsulating layer 2313 has been patterned to reveal the electrode 2308and to form an insulating layer 2316 including a generally crownedsurface. The electrode 2308 being sunken into the insulating layer 2316can help to reduce edge effects, which can increase uniformity of anelectric field emanating from the electrode 2308. The electrode 2308 canalso be spaced from tissue by an upper surface of the insulating layer2316, which can allow blood flow across the electrode 2308. In someexamples, the insulating layer 2316 may be omitted. In some examples, adual damascene structure can be formed in the insulating layer 2307 andthe electrode 2308 can be formed in the insulating layer 2307, which canbe shaped to have a crowned surface. A wide variety of layers, patterns,and processes can be used to form the described components and othercomponents. For example, a resistor layer may be patterned proximate tothe substrate 2301, which can provide localized heating, which can causea shape-memory substrate to locally deform to an austenitic state.

Although not meant to be limiting, the following electrode dimensionsmay be adequate to generate a hemodynamic response due toneurostimulation. About half of the electrodes can be assumed to contactthe vessel and about half of the electrodes can be assumed to be exposedto low impedance blood flow. Referring again to the elevational view ofFIG. 23G as an example, the length of an electrode 2806 may be betweenabout 1 mm and about 3 mm (e.g., about 1 mm, about 1.5 mm, about 2 mm,about 2.5 mm, about 2 mm, ranges between such values, etc.); the widthof an electrode 2806 may be between about 1 mm and about 4 mm (e.g.,about 1 mm, about 2 mm, about 3 mm, about 4 mm, ranges between suchvalues, etc.); and the spacing between electrodes 2806 may be betweenabout 2 mm and about 8 mm (e.g., about 2 mm, about 3 mm, about 4 mm,about 5 mm, about 6 mm, about 7 mm, about 8 mm, ranges between suchvalues, etc.). The spacing between electrodes may refer to the distancebetween a distal end of a proximal electrode and the proximal end of adistal electrode, the distance between the center of one electrode andthe center of another electrode, and/or the distance betweencircumferentially or laterally spaced electrodes. The electrode 2308 maybe configured to maintain a charge density at an electrochemicallystable level less than about 400 μC/cm² for Pt/Ir^(1,2,3). Referringagain to FIG. 23G as an example of an annular electrode, the electrodes2394 may have a diameter of about 7 Fr (approx. 2.3 mm), have a lengthof about 1.5 mm, and be spaced by about 8 mm. In some examples, theelectrodes 2394 may have a length between about 1 mm and about 3 mm(e.g., about 1 mm, about 1.5 mm, about 2 mm, about 2.5 mm, about 2 mm,ranges between such values, etc.), a diameter between about 0.5 mm andabout 1.5 mm (e.g., about 0.5 mm, about 0.75 mm, about 1 mm, about 1.25mm, about 1.5 mm, ranges between such values, etc.), and spacing betweenabout 1 mm and about 3 mm (e.g., about 1 mm, about 1.5 mm, about 2 mm,about 2.5 mm, about 2 mm, ranges between such values, etc.).

The target nerve may be a very small target to capture vianeurostimulation. Electrodes, most likely the cathode, may need to bevery close to the nerve, if not by depth than by lateral positioning.One option to provide close lateral positioning is to have aneffectively infinite number of electrodes, or at least an electrodematrix that can cover all possible areas of the nerve with respect tothe target vessel. Another option to provide close lateral positioningis to provide repositionable electrodes, for example electrodes in amatrix that can be extended, retracted, and/or rotated.

FIG. 23M shows an example electrode matrix. The electrodes are spacededge-to-edge by about 2 mm proximal-distal and superior-inferior. Theinitial target area estimate may be as large as 15 mm superior-inferiorand 19 mm laterally. In some examples, for example as illustrated inFIG. 23M, an electrode matrix has these dimensions, which mayeffectively behave as an infinite number of electrodes in view of thesize of the target area. In some examples, an electrode matrix may havesmaller dimensions and may be rotated and/or longitudinally moved.Although illustrated in two dimensions in FIG. 23N, in some examples,the electrode matrix may take a three-dimensional shape (e.g.,conforming to an inside wall of a blood vessel). In certain suchexamples, the electrode matrix may cover between about 15° and about360° of the circumference of the vessel wall (e.g., about 15°, about30°, about 45°, about 60°, about 75°, about 90°, about 105°, about 120°,about 180°, about 210°, about 270°, about 300°, about 360°, rangesbetween such values, etc.). The e values indicate the percent abovebaseline hemodynamic response. The value of e₁ between electrodes C5 andC4 was 3.0%. The value of e₂ between electrodes C4 and C3 was 12.1%. Thevalue of e₃ between electrodes D6 and D5 was 18.5%. The value of e₄between electrodes D5 and D4 was 40.2%. The value of es betweenelectrodes D4 and D3 was 23.7%. The value of e₆ between electrodes E5and E4 was 0%. The value of e₇ between electrodes E5 and E3 was 0.3%.The value of e₈ between electrodes C4 and D4 was 28.9%. The value of e₉between electrodes C3 and D3 was 21.1%. The value of e₁₀ betweenelectrodes C2 and D2 was 7.1%.

Hemodynamic response decreases by approximately half as the excitationis moved from one pair of electrodes to the adjacent space pair. Whencenter-to-center spacing is 3.5 mm, this would suggest that once anoptimum target has been determined, a movement of the electrode matrixon the order of 3.5 mm would significantly decrease the hemodynamicresponse. Certain fixation systems described herein can limit electrodemovement to less than an order of magnitude of this variation (e.g.,about 0.035 mm total electrode migration), over the therapy applicationperiod. In some examples, a fixation system can inhibit electrodemigration to be less than about 1 mm, less than about 0.5 mm, less thanabout 0.25 mm, less than about 0.1 mm, less than about 0.075 mm, lessthan about 0.05 mm, less than about 0.035 mm, less than about 0.025 mm,or less than about 0.015 mm, with the lower limit of such “less than”ranges being 0 mm.

In some examples, an electrode matrix (e.g., including a portion of anelectrode utilized for calibration stimulation and/or therapeuticstimulation) may have an area between about 10 mm² and about 15 mm²(e.g., about 10 mm², about 11 mm², about 12 mm², about 13 mm², about 14mm², about 15 mm², ranges between such values, etc.). In some examples,an electrode matrix may have an area between about 10 mm² and about 300mm² (e.g., about 10 mm², about 50 mm², about 100 mm², about 150 mm²,about 200 mm², about 250 mm², about 300 mm², ranges between such values,etc.).

FIG. 24A illustrates an example of a fixation system 2400. The fixationsystem 2400 comprises a fixation structure 2402 and fixation mechanisms2404. The fixation structure 2402 may comprise, for example, a hypotubethat has been cut and shape set into a plurality of arms, wires thathave been shape set into a plurality of arms, and the like. The arms maybe the same or different (e.g., as illustrated in FIG. 24A, one arm mayflex upward). The fixation mechanisms 2404 may comprise, for example,points or barbs pointing radially outward from the fixation structure2402. The fixation mechanisms 2404 may be integral with the fixationstructure 2402 or coupled to the fixation structure 2402.

FIGS. 24B and 24C illustrate the fixation system 2400 of FIG. 24Ainteracting with a catheter 2406. As the fixation structure 2402 and thecatheter 2406 are moved longitudinally to each other (e.g., retractingthe fixation structure 2402 and/or advancing the catheter 2406), thearms of the fixation structure 2402 move radially inward. The fixationmechanisms 2402 may injure tissue during this interaction. The fixationmechanisms 2402 may catch on the catheter 2406 (e.g., starting at theend of the catheter 2406) and may dig into the catheter 2406 to formtrenches 2408, which may release catheter residue, use more longitudinalinteraction force, etc. In some examples, the catheter 2406 may includegrooves or channels configured to accommodate the fixation mechanisms,although radial outward force provided by the fixation structure 2402may still tissue injury and/or trenches 2408.

FIG. 25A is a perspective view of another example of a fixation system2500. FIG. 25B is a side elevational view of the fixation system 2500 ofFIG. 25A. FIG. 25C is an end view of the fixation system 2500 of FIG.25A. The fixation system 2500 comprises a fixation structure 2502 and afixation mechanism 2504. The fixation structure 2502 may comprise, forexample, a hypotube that has been cut and shape set, a ribbon that hasbeen shape set, and the like. The fixation mechanisms 2504 may comprise,for example, points or barbs pointing radially outwardly in a deployedposition or state and pointing radially inwardly in a constrainedposition or state due to the fixation structure 2502 comprising arotation or twist 2510. The rotation 2510 may be between about 60° andabout 300° (e.g., about 60°, about 90°, about 120°, about 150°, about180° (e.g., as illustrated in FIGS. 25A-25C), about 210°, about 240°,about 270°, about 300°, ranges between such values, and the like). Insome examples, the fixation structure 2502 comprises a shape memorymaterial and the rotation 2510 is imparted as at least part of a shapeset. The fixation mechanism 2504 may be integral with the fixationstructure 2502 or coupled to the fixation structure 2502.

FIGS. 25D and 25E illustrate the fixation system 2500 of FIG. 25Ainteracting with a catheter 2506. As the fixation system 2500 is movedlongitudinally relative to the catheter 2506, the fixation structure2502 rotates relative to the longitudinal axis. The fixation mechanism2502, which faces radially inward in the catheter 2506, rotates to faceradially outward upon extension out of the catheter 2506. Conversely,the fixation mechanism 2502, which faces radially outward out of thecatheter 2506, rotates to face radially inward upon retraction into thecatheter 2506. The fixation structure 2502 may be radially outwardlybiased to push against the lumen of the catheter 2506.

FIGS. 25F illustrates an example of a catheter 2506 comprising a lumen2512 having a shape configured to accommodate the fixation structure2502 and the fixation mechanism 2504. The lumen 2512 may, for example,comprise a pentagon configured to interact with three sides of arectangular fixation structure 2502 and a pointed fixation mechanism2504 extending from the other side of the fixation structure 2502. Othershapes of the lumen 2512 are also possible. For example, referring againto FIG. 25C, the lumen 2512 may comprise a generally arcuate shapeconfigured to interact with two sides of a rectangular fixationstructure 2502.

FIGS. 25G-25J illustrate an example deployment of the fixation structure2502 and the fixation mechanism 2504 out of the lumen 2512 of thecatheter 2506 of FIG. 25F. As shown in FIG. 25G, as the fixationstructure 2502 and fixation mechanism 2504 is initially deployed out ofthe lumen 2512 of the catheter 2510, with the twist 2510 still in thelumen 2512, the fixation mechanism 2504 faces radially inwardly. Asshown in FIG. 25H, when the twist 2510 is out of the lumen 2512, thefixation mechanism 2504 can start to turn radially outward. FIG. 25Ishows the fixation mechanism 2504 continuing to turn radially outward asthe twist 2510 is further from the lumen 2512, which allows the shape ofthe fixation structure 2502 to rotate. FIG. 25J shows the fixationmechanism 2504 facing radially outward or standing proud. In someexamples, the fixation structure 2502 and fixation mechanism 2504 may bedeployed out of an end of the catheter 2506. In some examples, thefixation structure 2502 and fixation mechanism 2504 may be deployed outof a side of the catheter.

FIG. 26A is a side elevational view of an example of a catheter system2600. The catheter system 2600 comprises a fixation system 2602 and anelectrode system 2604. The fixation system 2602 may comprise radiallyoutwardly extending features, for example as described herein. Theelectrode system 2604 may comprise a scaffold and electrodes, forexample as described herein. In the example illustrated in FIG. 26A, theelectrode system 2604 includes tethers 2605, which can help withpositioning in and out of a sheath 2606. The fixation system 2602 isdistal to the electrode system 2604.

FIGS. 26B-26H illustrate an example method of deploying the cathetersystem 2600 of FIG. 26A. This is an example of an over-the-wire orstepwise placement method in which a balloon is used to place aguidewire, which provides a rail to guide components to a targetlocation.

In FIG. 26A, a Swan-Ganz catheter 2612 comprising a distal balloon 2614is floated to a target area. For example, a Swan-Ganz catheter 2612 maybe inserted into an access point of an internal jugular vein (left orright) in an uninflated state, then inflated, after which it can becarried by blood flow to a target site such as a pulmonary artery (left,right, or trunk). In some examples, the Swan-Ganz catheter 2612 is a 8Fr Swan-Ganz catheter having a 1.5 cm³ balloon, for example as isavailable from Edwards Lifesciences Corp. In FIG. 26C, a guidewire 2616is routed through a lumen of the Swan-Ganz catheter 2612 until thedistal end of the guidewire 2614 protrudes from the distal end of theSwan-Ganz catheter 2612. In FIG. 26D, the Swan-Ganz catheter 2612 iswithdrawn, leaving the guidewire 2616.

In FIG. 26E, a fixation catheter 2620 including the fixation system 2602at the distal end of a tether 2622 is advanced over the guidewire 2616and the fixation system 2602 is deployed. In some examples, the fixationcatheter 2620 is 8 Fr or 9 Fr. In FIG. 26F, the guidewire 2616 and thefixation catheter 2620 are withdrawn, leaving the fixation system 2602and the tether 2622 in place. In FIG. 26G, the sheath 2606 including theelectrode system 2604 is advanced over the tether 2622. In someexamples, the distance between the fixation system 2602 and the distalend of the sheath 2606 may be known, for example, from proximalmarkings. In FIG. 26H, the sheath 2606 is proximally retracted to deploythe electrode system 2604. In some examples, the electrode system 2604has a diameter of about 25 mm in the expanded state. The fixation system2602 and the electrode system 2604 may be coupled, for example at aproximal end. In some examples, the electrode system 2604 is able tomove relative to the fixation system 2602. Deploying catheters in aserial fashion (target location, then fixation system, then electrodessystem) can allow the catheter diameters to be small and flexible (e.g.,compared to an all-in-one or combination systems).

To withdraw the system, the steps may be reversed with some access stepsomitted. For example, the sheath 2606 may be distally advanced tocapture the electrode system 2604, for example due to the tethers 2605helping to pull the electrode system 2604 into the sheath 2606. Thesheath 2606 including the electrode system 2604 may then be withdrawn.The fixation catheter 2620 may be advanced over the tether 2622 tocapture the fixation system 2602, and the fixation catheter 2620including the fixation system 2602 may be withdrawn. The dimensions inthis example method are not meant to be limiting to any particularexample (see, for example, other dimensions provided herein for thesetypes of elements).

In some examples, a single catheter could include the fixation system2602 and the electrode system 2604 (e.g., allowing integration of FIGS.26E-26H). In some examples, the fixation system 2602 may be proximal tothe electrode system.

In some examples, the fixation system 2602 can be anchored in the distalright pulmonary artery (e.g., delivering the fixation catheter 2620 asfar as it can extend before deploying the fixation system 2602), and theelectrode system 2604 can be deployed in a more proximal position.Fixation in the distal right pulmonary artery may be more stable and/orrepeatable. The electrode system 2604 could be repositionable (e.g.,able to slide, rotate) to map without modifying the position of thefixation system 2602. A proximal hub could comprise a locking mechanismto hold the electrode system 2604 in a set position and/or an appositiondevice could secure the electrode system 2604.

FIG. 27A is a perspective view of another example of a fixation system2700. FIG. 27B is an elevational view of a portion of the fixationsystem 2700 of FIG. 27A. The fixation system 2700 comprises a fixationstructure 2702 and a fixation mechanism 2504. The fixation structure2702 may comprise, for example, a hypotube that has been cut and shapeset, a ribbon that has been shape set, and the like. The fixationstructure 2702 may be shape set, for example to flare radially outwardwhen not constrained by a catheter 2706. The fixation mechanism 2704 isillustrated as comprising a conical structure, but may comprise othershapes, for example, points or barbs. The fixation mechanism 2704 iscoupled to the fixation structure 2702 by a fixation arm 2703. In someexamples, the fixation arm 2703 may be integral or monolithic with thefixation structure 2702, for example being milled from the fixationstructure 2702. In some examples, the fixation arm 2703 is the samethickness as the fixation structure 2702. In some examples, the fixationarm 2703 a different thickness than the fixation structure 2702, forexample to provide different collapsing characteristics. In someexamples, the fixation arm 2703 may formed separately and then coupledto the fixation structure 2702, for example by welding, soldering, etc.to the fixation structure 2702 in a hole or aperture that has beenmilled in the fixation structure 2702. In some examples, the fixationarm 2703 may be integral or monolithic with the fixation mechanism 2704,for example both being milled from a same piece of material (e.g., thefixation structure 2702). In some examples, the fixation arm 2703 mayformed separately and then coupled to the fixation mechanism 2704, forexample by welding, soldering, etc. The fixation arm 2703 is configuredto flare radially outward of the fixation structure 2702 when notconstrained. The fixation arm 2703 comprises a curved shape such that,when the fixation arm 2703 is constrained, for example by a catheter2706, the fixation mechanism 2704 is radially inward of or below theouter surface of the fixation structure 2702.

FIGS. 27C-27F illustrate the fixation system 2700 of FIG. 27A beingretracted after engagement with tissue 2708. Prior to the stateillustrated in FIG. 27C, the system 2700 was advanced to a fixationsite. The system 2700 was advanced out of the catheter 2706, for exampleout of the side or out of the end of the catheter 2706. When notconstrained by the catheter 2706, the fixation structure 2702 may flareradially outwardly. When not constrained by the catheter 2706, thefixation arm 2703 may flare radially outwardly from the fixationstructure 2702 and engage the tissue 2708. For example, the fixation arm2703 may pivot or rotate at the point where the fixation arm 2703contacts the fixation structure 2702. In FIGS. 27D-27F, a catheter 2706advancing over the fixation arm 2703 causes the fixation arm 2703 toflex radially inwardly until, as shown in FIG. 27F, the fixationmechanism 2704 is radially inward of or below the outer surface of thefixation structure 2702. In FIG. 27D, the fixation structure 2704 ispulled out of the tissue 2708 in the same direction as the initialinteraction with the tissue 2708, which can be gentle on the tissue 2708(e.g., reducing or preventing endothelial damage such as snagging,tearing, scratching, etc.).

FIG. 27G is an elevational view of yet another example of a fixationsystem 2750. The fixation system 2750 is similar to the fixation system2700, comprising a fixation structure 2752, a fixation mechanism 2754,and a fixation arm 2753, but the fixation arm 2753 is not configured tomove relative to the fixation structure 2752. FIG. 27G also illustratesthe fixation arm 2753 having an end shape configured to correspond to ashape of the base of the fixation mechanism 2754 (e.g., annular for aconical fixation mechanism 2754). FIG. 27H is a side view of thefixation system 2750 of FIG. 27G. The fixation arm 2753 is spacedradially inward from the outer surface of the fixation structure 2752 bya first cavity 2755. The fixation arm 2753 is spaced radially outwardfrom the inner surface of the fixation structure 2752 by a second cavity2757. When the fixation system 2750 is pressed against tissue, some ofthe tissue may enter the cavity 2755 and interact with the fixationmechanism 2754. The second cavity 2757 may allow the fixation arm 2753to bend or flex radially inward. When the fixation system 2750 is priedaway from tissue, for example by retracting the fixation structure 2752into a catheter, the tissue may exit the cavity 2755 and stopinteracting with the tissue.

FIG. 27I is a side view of still another example of a fixation system2760. The fixation system 2760 is similar to the fixation system 2750,comprising a fixation structure 2762, a fixation mechanism 2764, and afixation arm 2763, but the fixation arm 2763 is not configured to flex.The fixation arm 2763 is spaced radially inward from the outer surfaceof the fixation structure 2762 by a first cavity 2755, but is not spacedradially outward from the inner surface of the fixation structure 2762by a second cavity. When the fixation system 2760 is pressed againsttissue, some of the tissue may enter the cavity 2765 and interact withthe fixation mechanism 2764. The lack of a second cavity may allow thefixation arm 2763 to remain solid, which may increase likelihood oftissue engagement. When the fixation system 2760 is pried away fromtissue, for example by retracting the fixation structure 2762 into acatheter, the tissue may exit the cavity 2765 and stop interacting withthe tissue.

FIG. 28A is a side view of an example of a fixation system 2800. Thefixation system 2800 comprises a fixation structure 2802, distalfixation mechanisms 2804 a, and proximal fixation mechanisms 2804 b. Thedistal fixation mechanisms 2804 a extend distally from the distal end ofthe fixation structure 2802 (e.g., distal ends of cells formed by strutsof the fixation structure 2802). The distal fixation mechanisms 2804 aflare radially outward in an expanded position. Upon retraction of thefixation structure 2802, for example into a catheter, the distalfixation mechanisms 2804 a flex radially inwardly from proximal todistal. The proximal fixation mechanisms 2804 b extend proximally froman intermediate portion of the fixation structure 2802 (e.g., proximalends of cells formed by struts of the fixation structure 2802). Theproximal fixation mechanisms 2804 b flare radially outward in anexpanded position. Upon retraction of the fixation structure 2802, forexample into a catheter, the proximal fixation mechanisms 2804 b flexradially inwardly as described in further detail herein. FIG. 28B is anexpanded view of the circle 28B in FIG. 28A, which better illustratesthe radially outward flexing of the proximal fixation mechanism 2804 b(e.g., versus the other contours of the fixation system 2800). Thefixation mechanisms 2804 are shape-set to protrude outside the wall ofthe fixation structure 2802.

FIG. 28C is a partial elevational view of the fixation system 2800 ofFIG. 28A. The proximal fixation mechanisms 2804 b are coupled to thefixation structure 2802 at attachment points 2812. The proximal fixationmechanisms 2804 b may be integral or monolithic with the fixationstructure 2802 (e.g., cut from the same hypotube, for example asdescribed with respect to FIG. 28F). The strands proximal to theattachment points 2812 are tethers 2808 comprising twists or bends 2810.When a hypotube is cut to form an attachment point 2812, a proximalfixation mechanism 2804 b, a tether 2808, cell struts, etc., theattachment point 2812 naturally becomes radially offset (e.g., because alarge mass naturally wants to remain straight) such that the proximalfixation mechanism 2804 b is slightly radially inward of the cell strutsand the tether 2808. A similar phenomenon occurs at the connectingstruts 2817 (FIG. 28A) between cells. The cut hypotube may be shape setincluding, without limitation, flaring the fixation structure 2802radially outward from proximal to distal, flaring the fixationmechanisms 2804 a, 2804 b radially outward from the fixation structure2802 (e.g., so the fixation mechanisms 2804 a, 2804 b stand proudcompared to the fixation structure 2802), and twisting the tethers 2808.

FIG. 28D shows an example of a radiopaque marker 2814 coupled to aproximal fixation mechanism 2804 b. The radiopaque marker 2814 maycomprise a band, an identifiable shape (e.g., a rectangle, circle,etc.). In some examples, the radiopaque member 2814 protrudes outwardfrom the proximal fixation mechanism 2804 b. In some examples, theradiopaque member 2814 is flush with the proximal fixation mechanism2804 b. Other portions of the fixation system 2800 may comprise aradiopaque marker (e.g., other proximal fixation mechanisms 2804 b,distal fixation mechanisms 2804 a, fixation structure 2802, tethers2810, etc.)

FIG. 28E shows an example of a hole or opening or aperture 2816 in aproximal fixation mechanism 2804 b. In some examples, the hole 2816 maybe used to attach other components (e.g., radiopaque markers, fixationelements such as conical members, barbs, fixation arms, etc.), such asby crimping, welding, etc. Attaching certain structures may providebetter control of certain properties, for example shape-setting. In someexamples, the hole 2816 may help to capture tissue, for example theedges of the hole 2816 apposing tissue penetrating the hole 2816.

FIG. 28F is a flattened view of an example of a hypotube cut pattern2820. The cut pattern 2820 includes tethers 2808, attachment points2812, proximal fixation mechanisms 2804 b including holes 2816, fixationstructure 2802, and distal fixation mechanisms 2804 a. The cut patternalso shows ramped or tapered areas 2822. The tapered areas 2822 canengage the distal end of a catheter during retraction, and may help withturning the proximal fixation mechanisms 2804 b. In some examples, itmay be possible to cut a sheet and roll the sheet into a tube (e.g.,initially shape setting into a cylinder and then shape setting, ordirectly shape setting). The cut hypotube may be shape set, for exampleinto the shape shown in FIG. 28A.

FIG. 28G is an expanded view of the dashed square 28G in FIG. 28F. Inaddition to the other manners of shape setting described herein, a strut2824 adjacent to the proximal fixation mechanism 2804 b may be bent atan angle. FIG. 28H is a side view of the strut 2824 of FIG. 28G. Theproximal end 2826 of the proximal fixation mechanism 2804 b and thedistal end 2828 of the proximal fixation mechanism 2804 b are shown indotted lines behind the strut 2824. FIG. 28I is a side view of theproximal fixation mechanism 2804 b being bent radially outward. FIG. 28Jis a side view of the proximal fixation mechanism 2804 b being bentradially outward and the strut 2824 being bent at a bend point 2830.Referring again to FIG. 28H, the length x of the proximal fixationmechanism 2804 b is shown. In some examples, the bend point 2830 isabout 50% of x±20% (e.g., measured from the proximal end 2826 or thedistal end 2828, about 20% of x, about 30% of x, about 40% of x, about50% of x, about 60% of x, about 70% of x, ranges between such values,etc.). The more proximal the bend point 2830, the more the proximalfixation mechanism 2804 b protrudes radially outward. The more distalthe bend point 2830, the less the proximal fixation mechanism 2804 bprotrudes radially outward. The angle of the portion of the strut 2824proximal to the bend point 2830 relative to the portion of the strut2824 distal to the bend point 2830 is between about 20° and about 50°(e.g., about 20°, about 30°, about 40°, about 50°, ranges between suchvalues, etc.). In some examples, the distance y between the distal endof the proximal fixation mechanism 2804 b and the portion of the strut2824 distal to the bend point (or, in FIG. 28I, the unbent strut 2824)in an unconstrained state is between about 0.02 inches and about 0.06inches (e.g., about 0.02 inches, about 0.03 inches, about 0.04 inches,about 0.05 inches, about 0.06 inches, ranges between such values, etc.),although factors such as vessel diameter, the length x, etc. mayinfluence the distance y.

FIG. 28K is a side view of the strut 2824 being bent at the bend point2830. In contrast to FIG. 28J, the proximal fixation mechanism 2804 b isnot bent, although other parameters (e.g., bend angle, location of thebend point 2830, the distance y, etc.) may remain the same.

FIGS. 28L-28O show the proximal fixation mechanisms 2804 b rotatinginwardly during retrieval into a catheter 2806. In FIG. 28L, thefixation system 2800 is fully deployed. The proximal fixation mechanisms2804 b stand proud. The distal fixation mechanisms 2804 a also standproud, providing bidirectional fixation. In FIG. 28M, the fixationsystem 2800 is starting to be withdrawn into the catheter 2806. Theproximal fixation mechanisms 2804 b still stand proud. In FIG. 28N, thefixation system 2800 is further withdrawn into the catheter 2806. Theproximal fixation mechanisms 2804 b still rotate inwardly as the distalend of the catheter 2806 interacts with the tapered portions 2822. InFIG. 28O, the fixation system 2800 is further withdrawn into thecatheter 2806. The proximal fixation mechanisms 2804 b except for thedistal ends are in the catheter 2806. No snagging, scratching, etc.occurred during retraction. Further retraction of the fixation system2800 would place the remainder of the fixation structure 2802 and thedistal fixation mechanisms 2804 a in the catheter 2806.

Having the proximal fixation mechanisms 2804 b pointed distally canallow for improved performance during retrieval of the fixation system2800 (e.g., lower probability of the proximal fixation mechanisms 2804 bor any other part of the fixation system 2800 getting snagged by thedistal end of the catheter 2806). Since the proximal fixation mechanisms2804 b articulate radially inwards upon retrieval, the proximal fixationmechanisms 2804 b can be included with little concern of scratchingand/or engaging the inner surface of the catheter 2806 during deploymentor retrieval. The degree of inward flex of the proximal fixationmechanisms 2804 b during retrieval can be controlled by, for example,the location of the bend point 2830, the attachment point 2812, and/orbending of the proximal fixation mechanisms 2804 b. The distal end cancomprise distal fixation mechanisms 2804 a, which can provide resistanceto distal motion.

In some examples, the fixation mechanisms described herein may take theform of a textured surface. For example, material may be added to and/orremoved from a fixation arm or a fixation structure to form a stippled,striped, rough, etc. surface. The texture may increase the surface area,which can increase the amount of tissue that is engaged.

FIG. 29A illustrates an example of a catheter system 2900. The cathetersystem 2900 comprises a sheath 2906, a first loop 2902 extending from adistal end of the sheath 2906, and a second loop 2904 extending from thedistal end of the sheath 2906. At least one of the first loop 2902 andthe second loop 2904 comprises a plurality of electrodes 2908. In someexamples, the catheter system 2900 comprises fixation features 2910(e.g., comprising atraumatic stiff loops).

FIGS. 29B-29F illustrate an example method of deploying the cathetersystem 2900 of FIG. 29A. In FIG. 29B, the sheath 2906 has been advancedpast the pulmonary valve 2928 into the pulmonary trunk 2922. Thepulmonary valve 2928 is a tricuspid valve. In some examples, the sheath2906 may have a shape configured to interact with the cuspids of thepulmonary valve 2928. The sheath 2902 may comprise a pressure sensorproximate to a distal end to help a user determine when the distal endof the sheath 2906 is distal to the pulmonary valve 2928. FIG. 29A alsoillustrates the right pulmonary artery 2924, the left pulmonary artery2926, the bifurcation 2925 between the right pulmonary artery 2924 andthe left pulmonary artery 2926, and a target nerve 2920 (e.g., the rightstellate CPN).

In FIG. 29C, the loops 2902, 2904 are deployed from the distal end ofthe sheath 2906. In some examples, the loops 2902, 2904 are deployedsubstantially simultaneously, which can reduce delivery complexity, forexample using a single actuation mechanism having a short deliverythrow. In some examples, the loops 2902, 2904 may be deployedsequentially or serially or staggered with either loop being deployedfirst, which can reduce the profile of the catheter system 2900. Theloops 2902, 2904 may be in any rotational orientation.

In FIG. 29D, the sheath 2906, with the loops 2902, 2904 deployed, isadvanced towards the bifurcation 2925. The loops 2902, 2904 self-orientinto the right pulmonary artery 2904 and left pulmonary artery 2906,regardless of the original rotational orientation of the loops 2902,2904. For example, the catheter system 2900 may rotate during distaladvancement in response to the loops 2902, 2904 interacting with theanatomy.

In FIG. 29E, the sheath 2906 is further distally advanced towards thebifurcation 2925. The loops 2902, 2904 may advance further into theright pulmonary artery 2924 and the left pulmonary artery 2926,respectively, but advancement is limited by the bifurcation 2925. InFIG. 29F, fixation features 2910 may optionally be deployed from thesheath 2906, for example proximate to the pulmonary valve 2928. Thefixation features 2910 may bias the sheath 2906 distally towards thebifurcation 2925, which can limit distal advancement. In some examples,the fixation features 2910 comprise a shape memory material such asnitinol. Blood flow is in the distal direction, which can help tomaintain the positions of the loops 2906. In some examples, the sheath2906 may comprise features to interact with the blood flow (e.g., fins,a balloon, etc.).

The electrodes 2908 of the first loop 2902 and the electrodes 2908 ofthe second loop 2904 may be activated according to a predetermined orlogical sequence to determine which loop 2902, 2904 can modulate thetarget nerve 2910. The electrodes 2908 of the selected loop may be usedfor neuromodulation and the electrodes 2908 of the other loop may bedeactivated.

In some examples, only the first loop 2902 comprises electrodes 2908.The second loop 2904 may still provide self-orientation and interactionwith the bifurcation 2925. The electrodes 2908 of the first loop 2902may be activated according to a predetermined or logical sequence todetermine if the first loop 2902 can modulate the target nerve 2910. Ifthe first loop 2902 is determined to not be able to modulate the targetnerve 2910, the catheter system 2900 may be repositioned (e.g.,including rotating, for example) 180° so that the first loop 2902 is inthe other of the right pulmonary artery 2924 and the left pulmonaryartery 2926.

In some examples, rather than loops 2902, 2904, a catheter systemcomprises two fingers having pigtail ends. The pigtail ends may providethe same benefits, for example bifurcation interaction, as the loops2902, 2904, and reduce potential issues such as poking the vasculature,bending, etc.

In some examples, neither of the loops 2902, 2904 comprises electrodes2938. In certain such examples, the electrodes 2938 may be disposed onthe sheath 2906. FIG. 29G illustrates an example of a catheter system2930. The catheter system 2930 comprises a sheath 2906, a first loop2902 extending from a distal end of the sheath 2906, and a second loop2904 extending from the distal end of the sheath 2906. The sheath 2906comprises a plurality of electrodes 2938. In some examples, the cathetersystem 2930 comprises fixation features 2910 (e.g., comprisingatraumatic stiff loops). The loops 2902, 2904 may inhibit or preventdistal migration and/or the fixation features 2910 may inhibit orprevent proximal migration. The catheter system 2930 may be positionedas described with respect to the catheter system 2900, for examplepassing distal to the pulmonary valve, deploying the loops 2902, 2904,and advancing towards a bifurcation where one loop 2902 extends into onebranch vessel and the other loop 2904 extends into the other branchvessel.

The electrodes 2938 may be annular, partially annular, points, etc. Insome examples, for example in which the electrodes 2938 are on one sideof the sheath 2906, the electrodes 2938 may be activated according to apredetermined or logical sequence to determine if the target nerve iscaptured. If the target nerve is not captured, the catheter system 2930may be repositioned (e.g., including rotating, for example) 180° so thatthe first loop 2902 is in the other of the right pulmonary artery 2924and the left pulmonary artery 2926. In some examples in which one orboth of the loops 2902, 2904 comprise electrodes 2908, the sheath 2908may comprise electrodes 2938.

In some examples, electrodes that are separate from the loops 2902, 2904may be deployed from the catheter 2906. For example, catheter systemsdescribed herein provide electrode matrices that can be deployed from aside of a catheter and/or an end of a catheter. In certain suchexamples, the loops 2902, 2904 can be used to orient and position thecatheter 2906 at a target site, and then an electrode matrix can bedeployed from the catheter 2906 at the target site.

In some examples, rather than being a plain loop, at least one of theloops 2902, 2904 may be modified, for example as described herein withrespect to other catheter systems. In some examples, each of the loops2902, 2904 may be modified differently.

FIG. 29H illustrates an example of a catheter system 2940. The cathetersystem 2940 comprises a sheath 2906, a first loop 2942 extending from adistal end of the sheath 2906, and a second loop 2904 extending from thedistal end of the sheath 2906. The first loop 2942 comprises a firstwire 2943 a and a second wire 2943 b. Each of the wires 2943 a, 2943 bcomprises electrodes 2948, forming an electrode matrix. Distal to thedistal end of the sheath 2906, the first wire 2943 a and the second wire2943 b are spaced to form a gap 2943 c that spaces the electrodes 2948on the wire 2943 a from the electrodes 2948 on the wire 2943 b. Morewires and electrodes are also possible. For example, a third wire mayextend between the first wire 2943 a and the second wire 2943 b. Theelectrodes 2948 are shown as button electrodes, but other types ofelectrodes are also possible (e.g., barrel, within a U-channel, etc.).

In some examples, the catheter system 2940 comprises fixation features2910 (e.g., comprising atraumatic stiff loops). The catheter system 2940may be positioned as described with respect to the catheter system 2900,for example passing distal to the pulmonary valve, deploying the loops2942, 2904, and advancing towards a bifurcation where one loop 2942extends into one branch vessel and the other loop 2904 extends into theother branch vessel.

FIG. 29I illustrates an example of a catheter system 2950. The cathetersystem 2950 comprises a sheath 2906, a first loop 2952 extending from adistal end of the sheath 2906, and a second loop 2904 extending from thedistal end of the sheath 2906. The first loop 2952 comprises a wirehaving an undulating or zig-zag or sinusoidal or wave shape. The firstloop 2952 comprises electrodes 2958 at peaks and valleys, forming anelectrode matrix. The electrodes 2958 may also or alternatively bepositioned between peaks and valleys. The first loop 2952 may compriseadditional wires and/or electrodes. For example, a second wire, whichmay be straight, sinusoidal, or another shape, may extend along thefirst wire. The electrodes 2958 are shown as button electrodes, butother types of electrodes are also possible (e.g., barrel, within aU-channel, etc.). In some examples, a sinusoidal shape may be in a planeconfigured to transversely appose a vessel wall. In certain suchexamples, electrodes are at sinusoidal peaks, which can provideincreased or optimum vessel wall contact. In some examples, a sinusoidalshape can increase rigidity, which can improve wall apposition, forexample compared to a straight shape.

In some examples, the catheter system 2950 comprises fixation features2910 (e.g., comprising atraumatic stiff loops). The catheter system 2950may be positioned as described with respect to the catheter system 2900,for example passing distal to the pulmonary valve, deploying the loops2952, 2904, and advancing towards a bifurcation where one loop 2952extends into one branch vessel and the other loop 2904 extends into theother branch vessel.

Several processes described herein are provided with respect to enteringthe pulmonary trunk and then advancing into the right pulmonary arteryand/or the left pulmonary artery, or more generically entering a main orafferent vessel and advancing into one or more efferent or branchvessels. In some examples, a catheter system may enter from a branchvessel and be advanced towards a main vessel and/or another branchvessel. For example, a catheter system may be inserted into the rightinternal jugular vein and advanced towards a superior vena cava. Foranother example, a catheter system may be inserted into the leftinternal jugular vein and advanced towards a left brachiocephalic vein.

FIG. 29J illustrates another example of a catheter system 2960. Thecatheter system 2960 comprises a sheath 2906 and a loop 2962. The loop2962 is configured to extend from a distal end of the sheath 2906 and tobend proximally back towards the sheath 2906. In some examples, forexample as described with respect to the catheter system 2900, the loop2962 may comprise electrodes. In some examples, the catheter system 2960comprises fixation features 2910 (e.g., comprising atraumatic stiffloops). For example as described with respect to the catheter system2930, the sheath 2906 comprises electrodes 2968. In some examples, thecatheter system 2960 comprises sheath electrodes 2968 and the electrodeson the loop 2962.

FIG. 29K illustrates another example of a catheter system 2965. Thecatheter system 2965 is similar to the catheter system 2960 except thatthe loop 2963 is configured to extend from a side of the sheath 2906,through an aperture 2907, and to bend proximally. In some examples, theaperture 2907 may comprise turning features such as a ramp.

FIGS. 29L-29N illustrate an example method of deploying the cathetersystem 2965 of FIG. 29K. The example method may also or alternatively beused to deploy the catheter system 2960 of FIG. 29J or other cathetersystems. The vasculature illustrated in FIGS. 29L-29N includes the leftinnominate vein or left brachiocephalic vein 2955, the left subclavianvein 2961, and the left internal jugular vein 2964, described in furtherdetail herein with respect to FIG. 2I, although other the method mayalso be appropriate for use at other vascular or other lumenbifurcations. The catheter systems can be adjusted to better interactwith a Y-shaped bifurcation, a T-shaped bifurcation, from an afferentvessel, from an efferent vessel, depending on the relative sizes of thevessels, etc. In some examples, such catheter systems can advantageouslypositively locate the catheter at anatomical junctions. Certain suchanatomical junctions may have known passing nerves, which can allow theuser to locate electrodes in a precise location with reduced or minimalor no visualization (e.g., fluoroscopy) and/or guidance (e.g., use of aguidewire and/or guide catheter). In some examples, the Y-shaped orT-shaped anatomy may help ensure that the catheter and electrodes remainfixed in place.

In FIG. 29L, the catheter system 2965 is in the left internal jugularvein 2964, which may the point at which the vasculature is accessed byan introducer. The catheter system 2965 is advanced towards the leftbrachiocephalic vein 2955. At least during advancing past the junctionof the left subclavian vein 2961 and the left internal jugular vein2964, the loop 2963 is deployed out of the sheath 2906. As the sheath2906 is advanced in the left internal jugular vein 2964, the loop 2963is inwardly compressed slides along the wall of the left internaljugular vein 2964.

In FIG. 29M, the catheter system 2965 is advanced far enough that theloop 2963 is unconstrained and able to outwardly expand to a set shape.In FIG. 29N, the catheter system 2965 is retracted until the loop 2963contacts the left subclavian vein 2961. The catheter system 2965 can berepeatably placed at the junction between the left subclavian vein 2961and the left internal jugular vein 2964. In some examples, placement canbe without fluoroscopy, for example using distance and/or tactilechanges to determine that the catheter system 2965 is properlypositioned. Fixation features 2910 may optionally be deployed from thesheath 2906, for example proximate to the junction in the left internaljugular vein 2964. The electrodes 2968 can be positioned along thesheath 2906 to capture a target nerve 2921. The target nerve 2921 maycomprise, for example, a thoracic cardiac branch nerve. In someexamples, the target nerve 2921 is a cervical cardiac nerve. Cervicalcardiac nerves may also or alternatively be targeted from the leftinternal jugular vein 2964. In some examples, the catheter system 2965comprises features that may help to capture a target nerve. For example,the sheath 2906 may comprise a curvature to bend towards the position2921, the catheter system 2965 may comprise a second loop comprisingelectrodes and configured to be deployed out of the distal end or theside of the sheath 2906 in a direction opposite the loop 2963, and/orthe electrodes 2968 may be longitudinally aligned with and/or distal tothe aperture 2907.

FIG. 30A is a perspective view an example of an electrode system 3000.The system 3000 comprises a catheter 3006, a framework 3002, and aplurality of electrodes 3008. FIG. 30B is a top plan view of a portionof the electrode system 3000 of FIG. 30A. The catheter 3006 comprises aproximal segment 3010 having a generally circular cross-section and adistal segment 3012 having a generally oval cross-section. The roundshape of the proximal segment 3010 can be useful, for example, to coupleto round proximal components such as luer fittings, other roundcatheters, etc. The oval shape of the distal segment 3012 can be useful,for example, to preferentially align near the target zone, which canreduce or minimize distance from the sheath 3006 to the target zone. Theoval shape of the distal segment 3012 can be useful, for example, toresist torque and rotation. The framework 3002 may comprise, forexample, two shape memory (e.g., nitinol) wires forming a zig-zag orundulating or sinusoidal pattern or serpentine to create a wave frame oraccordion shape. The framework 3002 can be substantially level orplanar, or can comprise a curve, for example to bias or conform to avessel wall. Leads or conductor wires coupling the electrodes 3008 to amodulation system can run along and/or through the framework 3002.

The electrodes 3008 comprise buttons coupled to the framework 3002. Insome examples, the electrodes 3008 have a diameter between about 1 mmand about 3 mm (e.g., about 1 mm, about 1.5 mm, about 2 mm, about 2.5mm, about 3 mm, ranges between such values, etc.). The electrodes 3008are longitudinally offset, as shown by the dashed lines in FIG. 30B, tosequentially nest in catheter 3006 the before deployment and/or uponretraction, which can reduce the profile of the catheter. In someexamples, at least some of the electrodes 3008 may be side-by-side. Insome examples, one side of the electrodes 3008 is insulated, which canprovide directional electrodes 3008. The electrodes 3008 may be coupledto the framework 3002 to inhibit rotation of the electrodes 3008, forexample keeping the surfaces of the electrodes 3008 generally level orplanar. Interaction with tissue such as a vessel wall may induce theframework 3002 to bend before inducing the electrodes 3008 to rotate.

FIG. 30C is a perspective view of another example of an electrode system3020. Similar to the system 3000, the system 3020 comprises a catheter3006, a framework 3002, and a plurality of electrodes 3028. FIG. 30D isa distal end view of the electrode system 3020 of FIG. 30C in acollapsed state. FIG. 30E is a distal end view of the electrode system3020 of FIG. 30C in an expanded state. The expanded state shown in FIGS.30C and 30E is partially expanded, as some electrodes 3028 remain in thecatheter 3006. A selected number of electrodes 3028 may be deployed asdetermined by the user (e.g., based on the subject's anatomy, theindication, etc.).

The electrodes 3028 comprise barrel-shapes coupled to the framework3002. The framework 3002 may include longitudinal segments rather thanpeaks to accommodate the lengths of the electrodes 3008, and the bendsin the framework 3002 can maintain longitudinal positioning of theelectrodes 3028. In some examples, the electrodes 3028 have a diameterbetween about 0.01 in and about 0.1 in (e.g., about 0.01 in, about 0.02in, about 0.03 in, about 0.04 in, about 0.05 in, about 0.06 in, about0.08 in, about 0.1 in, ranges between such values, etc.). In someexamples, the electrodes 3028 have a length between about 0.02 in andabout 0.2 in (e.g., about 0.02 in, about 0.03 in, about 0.04 in, about0.05 in, about 0.06 in, about 0.07 in, about 0.08 in, about 0.09 in,about 0.1 in, about 0.12 in, about 0.15 in, 0.2 in, ranges between suchvalues, etc.). The edge electrodes 3028 are laterally side-by-side,which can provide certain electrode combination patterns (e.g., asdiscussed with respect to FIGS. 32A-32D). In some examples, a centralelectrode 3028 can be a cathode and the four closest lateral electrodes3028 can be anodes. In some examples, the electrodes 3028 may belaterally offset (e.g., like the electrodes 3008). In some examples, acircumferential arc of the electrodes 3028 is insulated, which canprovide directional electrodes 3028. The electrodes 3028 may be coupledto the framework 3002 to inhibit rotation of the electrodes 3028, forexample maintaining uninsulated surfaces of the electrodes 3028 facing acertain direction. Other shapes of the electrodes 3028 are also possible(e.g., cylindrical, spherical).

The system 3020 comprises an optional core element 3024. The coreelement may, for example, help to carry conductor wires and/or tomaintain a shape of the framework 3002. In some examples, the coreelement 3024 comprises a round tube (e.g., a hypotube). In someexamples, the core element 3024 is flat or ribbon shaped, rectangular,oval, or other shapes. In some examples, the core element 3024 islaterally offset from a center of the framework 3002.

FIG. 30F is a plan view of yet another example of an electrode system3030. Similar to the system 3000, the system 3030 comprises a framework3002 and a plurality of electrodes 3038. The system 3030 comprises asheet or membrane or mesh 3032. In contrast to the systems 3000, 3020,the electrodes 3038 of the system 3030 are on the sheet 3032 comprisinga flexible material (e.g., polyimide, silicone). The sheet 3032 maycomprise, for example, a flex circuit including patterned conductorwires. The sheet 3032 may comprise, for example, a mesh such asdescribed with respect to FIG. 4C. The sheet 3032 holding the electrodes3038 can provide control of the relative positions and spacing of theelectrodes 3038.

The system 3030 optionally comprises a core element 3034. The framework3032 may be coupled to the core element 3034, for example as individualV-shaped segments. The sheet 3032 is coupled to the framework 3002, andoptionally to the core element 3034. In some examples, the framework3002 and the sheet 3034 wrap around the core element 3034 in a collapsedstate. The system 3030 can be delivered in a collapsed state without acatheter (e.g., tracking the core element 3034 over a guidewire ortether), for example if the sheet 3032 at least partially thermallyinsulates the framework 3002 such that thermal shape memory is slow totake effect. FIG. 30G is a distal end view of the electrode system 3030of FIG. 30F. In the deployed state, as best seen in FIG. 30G, the sheet3032 has a curved shape, which can help to hold the electrodes 3038against a vessel wall.

FIGS. 31A and 31B show example electrode combinations for nineelectrodes in a 3×3 matrix. Other numbers of electrodes and patterns ofmatrices can be used, and the 3×3 matrix is shown only for the sake ofdiscussion. In examples in which a power supply is external to thesubject, energy budget may be of less concern than accurate tissue nervetargeting. A sequence of combinations in which a first electrode iscathodic and a second electrode is anodic can be tested to see whichcombinations provide certain effects (e.g., effecting contractilityand/or not affecting heart rate). A subject could provide inputregarding pain, cough, general discomfort, tingling, and/or othersensations during the process to give the system feedback about whichelectrode combinations cause those effects. The contractility responsecould be measured, for example via a pressure sensor, accelerometer, orother contractility measurement, including external tools such as echoultrasound.

FIG. 31A shows an example sequence of twelve combinations in which oneelectrode is anodic and one electrode is cathodic. Each combination maybe operated, for example, 4 ms, followed substantially immediately bythe next combination in the sequence. The sequence may be repeated ifthe initial run was successful, for example about 50 ms (20 Hz) later.After running the sequence of tests 1-12, combinations of electrodesthat have an effect above or below a certain threshold may be identifiedfor use and/or non-use in calibration stimulation and/or therapeuticstimulation. This can automate the mapping of the nerve location andincrease or optimize stimulus response for efficacy and tolerance. FIG.32A shows that other combinations of these same electrodes are alsopossible, for example, with an electrode in the middle, diagonal, etc.The same sequence or a shorter sequence (e.g., comprising tests 1, 2, 7,and 8) may be used to verify positioning on a macro level (e.g., thatsome combination of electrodes in that matrix position providesstimulation), for example upon initial positioning, repositioning,and/or periodically to check for matrix migration.

In some examples, a monopolar mode in which one electrode in the matrixis made cathodic with an anodic body patch (or vice versa) on thesubject's chest, back, or arm can be used before bipolar combinations ofelectrodes to find nerve faster, and then bipolar or guarded bipolar orbullseye (e.g., as discussed herein) combinations can be used to moreselectively capture the nerve.

In some examples, a plurality of sequences may be available (e.g.,having at least one electrical parameter or electrode combinationsequence that is different). For example if a first sequence causes morethan a threshold number of undesired responses, a second sequence maystart, and so on. The system may return to an initial sequence based onresults of other sequences.

Sequences of combinations in which a plurality of electrodes arecathodic and one electrode is cathodic, in which one electrode is anodicand a plurality of electrodes are cathodic, and in which a plurality ofelectrodes are anodic and a plurality of electrodes are cathodic arealso possible.

Electrical stimulation can create noise on an ECG. Some parameters thatcan be used to reduce or minimize the stimulation-induced noise includestimulation vector, amplitude, pulse width, and/or frequency. FIGS.31Ci-31Cxi illustrate an example method of setting a stimulation vector.Prior to FIG. 31Ci, the electrode 3102 has been established as capableof capturing a nerve when used as a cathode, for example using a systemand/or technique described herein. A stimulation vector can be set by aline between the cathode 3102 and an electrode used as an anode. In someexamples, electrodes around the cathode 3102 are tested to find astimulation vector that is orthogonal to the primary ECG vector, whichis the physical vector between two ECG leads. The primary ECG vector canbe the ECG vector that is being displayed on the hospital monitor and/orthe ECG vector that is being used by the hospital monitoring system todetect abnormalities in the ECG, such as arrhythmias or otherundesirable changes. In some examples, the primary ECG vector can be theECG vector that is being monitored by another device that recordscardiac electrical activity, such as an implantable cardiacdefibrillator. Finding and setting a stimulation vector that isorthogonal to the primary ECG vector can, for example, reduce a quantityof stimulation noise interference seen on an ECG signal. Without beingbound by any particular theory, it is believed that the stimulationcreates an electric field that generates a voltage in the body that isrecorded across the ECG vector, so if the stimulation is parallel to theECG vector, then the stimulation field is additive to the field producedby cardiac electrical signal and produces noise that is detectable(e.g., visible) on the primary ECG signal.

If the stimulation vector is orthogonal to the ECG vector, and assumingan isotropic homogeneous medium in which the electrical conductivity isthe same in all directions, then no voltage is applied across the ECGvector and has no effect, produces no noise, and/or does not show up onan ECG signal. In practice, the human body comprises various tissuetypes and is not isotropic or homogeneous. Positioning the stimulationvector as orthogonal to the primary ECG vector as possible can result inreduced noise on ECG. If there is prior knowledge of a primary ECGvector, tests can be reduced to include or only include stimulationvectors that are approximately orthogonal to that vector. In someexamples, a trial and error process may be used to adjust thestimulation vector to reduce or minimize noise on ECG.

In FIG. 31Ci, a first electrode 3104 is used as an anode. In FIG. 31Cii,a second electrode 3106 is used as an anode. In FIG. 31Ciii, a thirdelectrode 3108 is used as an anode. In FIG. 31Civ, a fourth electrode3110 is used as an anode. In FIG. 31Cv, a fifth electrode 3112 is usedas an anode. In FIG. 31Cvi, a sixth electrode 3114 is used as an anode.In FIG. 31Cvii, a seventh electrode 3116 is used as an anode. In FIG.31Cviii, an eighth electrode 3118 is used as an anode. The electrodes3104, 3106, 3108, 3110, 3112, 3114, 3116, 3118 provide eight differentstimulation vectors roughly 360° around the electrode 3102. More orfewer electrodes can be used as anodes. Using more electrodes canprovide additional stimulation vectors, which can increase precision andhelp to reduce ECG signal interference. Using fewer electrodes mayprovide fewer stimulation vectors, but may reduce stimulation setupduration and may still be sufficient to identify a noise reducingstimulation vector. FIGS. 31Ci-31Cviii illustrate the anode marchingaround the cathode 3102. For the sake of this example, the configurationof FIG. 31Civ, in which the electrode 3110 is the anode, produced astimulation vector 3120 that produced the least amount of ECG signalinterference. This configuration may be used for therapeuticstimulation. In some examples, this configuration may be used as one ofmultiple factors in determining an electrode configuration used fortherapeutic stimulation.

In some examples, depending on the electrode array, additional anodetesting may be performed. In FIG. 31Cix, a ninth electrode 3122 is usedas an anode. In FIG. 31Cx, a tenth electrode 3124 is used as an anode.In FIG. 31Cxi, an eleventh electrode 3126 is used as an anode. Forexample, FIGS. 31Cix-31Cxi may be part of the original anode marching(e.g., all electrodes in an array may be tested). In some examples,FIGS. 31Cix-31Cxi may be tested based on the results of testing in FIGS.31Ci-31Cviii, which found that the stimulation vector 3120 reduced ECGsignal noise. For example, the testing shown in FIGS. 31Cix-31Cxi may beomitted if the stimulation vector produced by using the electrode 3104as anode produced the least ECG signal noise amongst FIGS. 31Ci-31Cviii.For the sake of this example, the configuration of FIG. 31Cx, in whichthe electrode 3124 is the anode, produced a stimulation vector 3128 thatproduced the least amount of ECG signal interference, even less than thestimulation vector 3120. This configuration may be used for therapeuticstimulation. In some examples, this configuration may be used as one ofmultiple factors in determining an electrode configuration used fortherapeutic stimulation. In some examples, FIGS. 31Cix-31Cxi may be partof the original anode marching (e.g., all electrodes in an array may betested). In general, the smaller the distance between the anode andcathode on the stimulation vector, the smaller the noise generated onthe ECG due to the field being more limited around the activestimulation electrodes. Monopolar stimulation with a far anode relativeto the cathode can induce the most noise on the primary ECG signal,whereas a tighter bipolar configuration with an anode in close proximityto a cathode might generate less stimulation noise on ECG.

Other stimulation settings that can impact ECG noise include amplitude,pulse width, and/or frequency. Stimulation noise on ECG may be reducedwhen relatively lower stimulation amplitudes and/or stimulation pulsewidths are utilized. If a therapeutic effect is maintained at adesirable level, reducing the stimulation amplitude and/or stimulationpulse width might help reduce noise on ECG. Using reduced stimulationamplitude and/or pulse width in addition to using an approximatelyorthogonal ECG vector may further reduce or minimize noise on ECG.Matching the stimulation frequency to the ECG monitor's notch filterfrequency, for example as described herein, in combination withreduction in stimulation amplitude and/or stimulation pulse widthsand/or with an orthogonal ECG vector can further reduce, minimize, oreliminate stimulation noise on ECG.

Therapeutic efficacy may be the primary consideration for electrodeselection. Cathode selection may be the primary driver of therapeuticefficacy such that selection of an anode for stimulation vectoring toreduce ECG noise and/or side effects may be compatible secondaryconsiderations. In some examples, ECG noise due to stimulation can also(e.g., in addition to stimulation vectoring orthogonal to the ECGvector) or alternatively be reduced using other systems and methodsdescribed herein.

In some examples, the system may utilize a method in which the differentanodes are tested in a non-marching sequence, for example by focusing inon particular anodes based on the results of testing other anodes. Forexample, the tests of FIGS. 31 vi-31 viii may be skipped if it isdiscovered that the stimulation vector produced by using the electrode3112 as an anode produces more interference than the stimulation vectorproduced by using the electrode 3110 as an anode. The system may thentest additional electrodes having similar stimulation vectors, such asthe electrodes 3122, 3124, as shown in FIGS. 31Cix and 31Cx (e.g.,omitting the electrode 3126 of FIG. 31Cxi).

In some examples, a user may use a combination of an image of theelectrode matrix in the subject (e.g., a fluoroscopic image), which canprovide some information about the orientation of the various electrodeswith respect to anatomy or each other, and knowledge of the positions ofthe ECG leads to skip testing of certain anodes. For example,cathode-anode combinations that appear to be substantially parallel tothe ECG vector may be skipped, and/or cathode-anode combinations thatappear to be substantially perpendicular to the ECG vector may beincluded or tested more. Users may appreciate limitations of certainimage types (e.g., providing two-dimensional images for athree-dimensional space) and suppress the reduction of testsaccordingly.

If the device that is used to set the stimulation parameters and/orgenerate the stimulation output has feedback on the primary ECG vector,the device can use the feedback to automatically identify stimulationparameters that reduce or minimize noise on ECG. For example, the leadsto the device may be attached to the same electrode as those that areused to generate the primary ECG vector. Stimulation parameters,including stimulation vector, amplitude, pulse width, and/or frequencymay be adjusted to reduce or minimize the noise on ECG and increase ormaximize the signal to noise ratio. Limits set by the user, such ascathode selection or amplitude upper and lower bounds, may be used tolimit the parameter set being tested.

FIGS. 32A-32D show example electrode combinations for twelve electrodesin a 3×4 matrix. The 3×4 matrix is an example, and other matrices arealso possible (for example, but not limited to, 2×2, 2×3, 2×4, 2×5, 3×3,3×5, 4×4, 5×5, reversals (e.g., 3×2 being a reversal of 2×3), etc.). Insome examples, the matrix may be irregularly shaped, for example, being2×2 and then 3×3. In FIGS. 32C and 32D, the middle column is offsetrelative to the left and right columns. The electrode combinations ofFIGS. 32A-32D may be called “guarded bipolar” combinations because thecathode is completely surrounded by anodes, or is at least not adjacentto a non-anodic cathode. In FIG. 32A, the cathodic electrode in row 2,column 2 is surrounded by anodic electrodes in row 1, row 3, and row 2,columns 1 and 3. In FIG. 32B, the cathodic electrode in row 4, column 2is surrounded by anodic electrodes in row 3, and row 4, columns 1 and 3.In FIG. 32C, the cathodic electrode column 2, second from the top issurrounded by anodic electrodes in column 1, first two from the top,column 3, first two from the top, and column 2, first and third from thetop. In FIG. 32D, the cathodic electrode column 2, first from the bottomis surrounded by anodic electrodes in column 3, first from the bottom,column 2, first from the bottom, and column 3, second from the bottom.Guarded cathodes (using two or more anodes) can allow for controllingthe spread of the electric field, which can provide a more efficientstimulation to the target nerve, and/or which can reduce spillover ofthe electric field to non-target nerves, which could cause unintendedside-effects.

In some examples, an electrode matrix can be used to electronicallyreposition the electrodes. For example, referring to FIG. 32A, if all ofthe anodes and cathodes are shifted down one row such that the cathodicelectrode in row 3, column 2 is surrounded by anodic electrodes in row2, row 4, and row 3, columns 1 and 3. Referring again to FIG. 31A,changing from test 3 to test 9, from test 1 to test 11, etc. could beconsidered electronic repositioning. Electrodes may thereby beelectronically repositioned in multiple directions. In electronicrepositioning, the electrode matrix itself does not move or migrate.Electronic repositioning may be used to counter unintended movement ormigration of the electrode matrix.

In some examples, the stimulation comprises an active biphasic waveformin which area under a curve is actively managed to be zero by forcing apulse in opposite charge over a longer duration by measuring charge. Insome examples, the stimulation comprises a passive biphasic waveform inwhich area under a curve is zero by allowing the charge to dissipatefrom the tissue.

In some examples, the stimulation comprises an amplitude between about 1mA and about 20 mA (e.g., about 1 mA, about 2 mA, about 3 mA, about 4mA, about 5 mA, about 6 mA, about 7 mA, about 8 mA, about 9 mA, about 10mA, about 15 mA, about 20 mA, ranges between such values, etc.). Loweramplitudes may advantageously have less penetration depth, which caninhibit or avoid stimulation of nerves or other tissue that is nottargeted. Higher amplitudes may advantageously be more likely to have atherapeutic effect. In some examples, the stimulation comprises a pulsewidth between about 0.5 ms and about 4 ms (e.g., about 0.5 ms, about0.75 ms, about 1 ms, about 1.25 ms, about 1.5 ms, about 1.75 ms, about 2ms, about 2.25 ms, about 3 ms, about 4 ms, ranges between such values,etc.). In some examples, lower amplitude (e.g., less than about 10 mA)can be used in combination with a pulse width according to astrength-duration curve to provide the desired effect. Lower amplitudesmay advantageously have less penetration depth, which can inhibit oravoid stimulation of nerves or other tissue that is not targeted. Higheramplitudes may advantageously be more likely to have a therapeuticeffect. In some examples, a lower amplitude (e.g., less than about 10mA) can be used in combination with a pulse width according to astrength-duration curve to provide the desired effect.

In some examples, the stimulation comprises a frequency between about 2Hz and about 40 Hz (e.g., about 2 Hz, about 5 Hz, about 10 Hz, about 15Hz, about 20 Hz, about 25 Hz, about 30 Hz, about 40 Hz, ranges betweensuch values, etc.). Lower frequencies (e.g., less than about 10 Hz) mayadvantageously have negligible effect on pain receptors that generallyrespond to much higher frequencies such that a subject is more tolerantof the therapy.

In some examples, the stimulation is ramped at a beginning and/or an endof the stimulation duration. For example, if stimulation duration is 10seconds, the initial stimulation burst may be about 50% based on atleast one parameter (e.g., ON duration, amplitude, pulse width,frequency, etc.), then increased or ramped up to 60%, 70%, etc. over thecourse of 2 seconds until reaching 100%. After 6 seconds at 100%, thestimulation may be decreased or ramped down to 95%, 90%, etc. over thecourse of 2 seconds until reaching 50%, after which the stimulation maybe turned off. Ramping up and/or down may reduce side effects, increasesubject tolerance, and/or avoid shocks to the system that may occur withan initial full burst. The duration of the ramp(s) may be based on apercentage of stimulation duration (e.g., 20% ramp up, 20% ramp down),absolute durations (e.g., 2 seconds ramp regardless of stimulationduration), or other factors. The ramp may be linear or take some otherfunction (e.g., decreasing steps for a ramp up, increasing steps for aramp down). In examples in which a ramp up and a ramp down are used, theramp up may be different than the ramp down (e.g., starting percentagemay be different than end percentage, ramp up duration may be differentthan ramp down duration, ramp up function may be different than rampdown duration, etc.).

FIG. 33A is a plot of contractility versus stimulation. Starting from abaseline contractility, the stimulation is turned ON for Time 1. Thereis some time delay for the stimulation to result in a change incontractility (e.g., about 10 to 20 seconds), after which contractilitysteadily climbs until reaching a fairly steady state. When contractilityis turned OFF in time 2, there is some time delay before thecontractility begins to decay. The decay delay when stimulation is OFFis longer than the delay when stimulation is ON. The time to ramp up toa baseline level during the decay is also less than from a baseline. Thedecay may also be reduced over time. Accordingly, the stimulation ON andOFF do not perfectly correlate to the durations when contractilitychanges.

In some examples, stimulation is turned ON for 5 seconds, followed bystimulation being turned OFF for 10 seconds. In some examples,stimulation is turned ON for 2 seconds, followed by stimulation beingturned OFF for 5 seconds. In some examples, stimulation is turned ON for10 seconds, followed by stimulation being turned OFF for 30 seconds. Insome examples, stimulation is turned ON until a substantially steadystate is achieved, followed by stimulation being turned OFF until acertain contractility is reached, at which point the stimulation isturned ON until the substantially steady state is again achieved, etc.Such an approach can reduce or minimize an effective dose. A duty cycleapproach in view of this discovery can reduce the amount of time thatstimulation is ON, which can reduce energy usage, maintain therapeuticeffect, and/or reduce side effects, which can increase patient comfortand tolerability. mistake

In some examples, a ramping feature could be used to slowly ramp theintensity of the stimulation ON and OFF, or to shut the stimulation OFFquickly. A ramping feature can allow the patient to adapt to stimulationand reduce sudden transitions. For example, at least one parameter(e.g., ON duration, amplitude, pulse width, frequency, etc.) could beslowly increased and/or decreased over time until building towards afinal value.

In some examples, for example for short term treatment, a duty cycle maycomprise alternating ON for 5 seconds and OFF for 5 seconds for 1 hour.In some examples, for example for short term treatment, a duty cycle maycomprise alternating ON for 5 seconds and OFF for 10 seconds for 1 hour.In some examples, for example for short term treatment, a duty cycle maycomprise alternating ON for 10 minutes and OFF for 50 minutes for 1hour. In some examples, for example for long term treatment, a dutycycle may comprise alternating ON for 1 hour and OFF for 1 hour for 1day. In some examples, for example for long term treatment, a duty cyclemay comprise alternating ON for 1 hour and OFF for 1 hour for 1 day. Insome examples, for example for long term treatment, a duty cycle maycomprise alternating ON for 1 hour and OFF for 23 hours for 1 day. TheON durations in long term treatment may include the cycling of the shortterm treatments. For example, if alternating ON for 1 hour and OFF for 1hour for 1 day, the durations in which stimulation is ON for 1 hour maycomprise alternating ON for 5 seconds and OFF for 5 seconds for that 1hour. In some examples, a plurality of different ON/OFF cycles may beused during a long term ON duration, for example 10 seconds ON and 10seconds OFF for 1 minute, then 1 minute ON and 5 minutes OFF for 10minutes, then 10 minutes ON and 50 minutes OFF for 4 hours, for a longterm ON duration of 4 hours and 11 minutes. Short term and/or long termON/OFF cycles may be at least partially based on a patient state (e.g.,awake or sleeping, laying down or upright, time since initialstimulation, etc.).

FIG. 33B is a plot of contractility versus stimulation using athreshold-based approach and an optimized duty cycle. Stimulation isturned ON and OFF for some duration. As noted above, the decay ofcontractility after the duration is reduced such that contractilityremains above a threshold for a certain duration. This duration may beknown or determined, for example by sensing contractility. The brokenline in FIG. 33B shows a time when the determination is made to restartthe stimulation cycle for another duration. This process may be repeatedfor the time that the subject is being treated, until a recalibration,etc.

FIG. 34 is an example process flow that can be used to implement a dutycycle method, for example as described with respect to FIGS. 33A and33B. Stimulation is turned ON for 5 seconds, then OFF for 5 seconds,then repeated for 10 minutes, after which stimulation is turned OFF forone hour. The process flow of FIG. 34 then begins. Starting with cardiacstimulation OFF, a physiologic signal is monitored. A baseline trend isstored. The current signal is checked for deviation from the trend by aphysician-set threshold (e.g., less than or greater than a certainquantity, percentage, etc.). If the current signal has not deviated, thecardiac stimulation remains OFF and the physiologic signal continues tobe monitored and the baseline trend stored until the current deviates.When the current deviates from the trend, cardiac stimulation is turnedON. A patient monitor report is sent to the physician. At periodicintervals, the physiologic signal is rechecked to see if the trend isback to baseline. If the trend is not back to baseline, the cardiacstimulation remains ON. If the trend is back to baseline, the cardiacstimulation is turned OFF and the process starts all over.

In some examples, the system comprises one or more of the following:means for modulation (e.g., an electrode or other type of stimulationcatheter or delivery device), means for fixation (e.g., barbs, prongs,anchors, conical structures, or other types of fixation mechanisms),means for sensation (e.g., a sensor integral with a catheter, on aseparate catheter, external to a subject), and means for calibration(e.g., predetermined or logical sequences of determining stimulationparameters).

Several examples of the invention are particularly advantageous becausethey include one, several, or all of the following benefits: (i)increasing contractility (e.g., left ventricle), (ii) not affectingheart rate or affecting heart rate less than contractility, (iii)providing an anchoring or fixation system to resist movement, (iv),and/or (x)

FIG. 35A schematically illustrates a mechanically repositionableelectrode catheter system 3500. The system 3500 comprises a proximalportion a handle or hub 3502. The handle 3502 includes a mechanicalrepositioning system 3504 including a track or channel or groove 3510and a knob 3512 slideable within the groove 3510. The system 3500further comprises a sheath 3506 and an electrode system 3508. Theelectrode system 3508 may be movable in and out of the sheath 3506. FIG.35A shows the electrode system 3508 already expanded out of the sheath3506. The knob 3512 is coupled to the electrode system 3508 such thatlongitudinal and/or rotational movement of the knob 3512 results incorresponding longitudinal and/or rotational movement of the electrodesystem 3508. The sheath 3506 may be separately anchored in thevasculature, for example as described herein, such that only theelectrode system 3508 moves upon movement of the knob 3512.

In some examples, longitudinal movement of the knob 3512 results in thesame or 1:1 longitudinal movement of the electrode system 3508. In someexamples, gears or other mechanical devices can be used to make themovement ratio more than 1:1 or less than 1:1. Pulleys and othermechanical devices can be used to reverse movement of the knob 3512.FIG. 35A shows a detent groove 3522 in the sheath 3506, which caninteract with a detent coupled to the electrode system 3508 and/or theknob 3512, for example as described with respect to FIG. 35B. In FIG.35A, the knob 3512 has already been longitudinally advanced enough, froma proximal position, that the electrode system 3508 is deployed out ofthe sheath 3506.

In some examples, the electrodes of the electrode system 3508 may bestimulated to test the effect of certain pairs of electrodes. If none ofthe electrodes pairs has an effect, the electrode system 3508 may bemoved using the repositioning system 3504 and the test rerun. In someexamples, a distal-most electrode pair may have the most effect, but notas large an effect as may have been expected. The electrode system 3508may be advanced distally to better test the effects of the electrodesdistal to the original site.

FIG. 35B illustrates the catheter system 3500 of FIG. 35A afterlongitudinal advancement. Compared to FIG. 35A, the knob 3512 haslongitudinally advanced a distance 3514. Movement of the knob 3512 canbe manual, electronic, mechanical, combinations thereof, and the like.The electrode system 3508 has also longitudinally advanced a distance3514. The electrode system 3508 is coupled to a detent 3520. Forexample, the detent 3520 may be coupled to a hypotube, a wire, etc. Whenthe detent 3520 reaches a certain longitudinal position, the detent 3520may extend into the detent groove 3522 in the sheath 3506. The extensionmay produce an audible click or other identifiable sound. In someexamples, a number of audible clicks (e.g., 1, 2, 3, or more) can informthe user that the electrode system 3508 is fully deployed. In someexamples, the detent interaction may be indicative that an event hasoccurred to provide deterministic position, for example longitudinaladvancement of a certain distance (e.g., a cm, an inch, etc.),longitudinal advancement enough to fully deploy the electrode system3508, longitudinal advancement to a rotational movement track, etc. Thesystem 3500 may comprise multiple detents 3520 and/or multiple detentgrooves 3522. In some examples, a detent system can inhibit undesired oraccidental movement of the electrode system 3508.

In some examples, rotational movement of the knob 3512 or movement ofthe knob 3512 transverse to longitudinal movement can result inrotational movement of the electrode system 3508 in the same rotationalor transverse direction. Twisting and turning of the sheath 3506 mayresult in a movement ratio that is not 1:1. The catheter system 3500 maycomprise a rotational hard stop to limit rotational movement of theelectrode system 3508, for example as described with respect to FIGS.35C and 35D.

FIG. 35C illustrates the catheter system 3500 of FIG. 35A afterlongitudinal advancement and rotation. FIG. 35D is a cross-sectionalview taken along the line 35D-35D of FIG. 35C. Compared to FIG. 35A, theknob 3512 has longitudinally advanced and rotated. The electrode system3508 has also longitudinally advanced and rotated. The rotation of theknob 3512 may be greater than the rotation of the electrode system 3508.In some examples, the system 3500 comprises a rotational hard stop 3524,for example in the sheath 3506. Even if the knob 3512 was able to rotatefurther in the track groove 3510, the hard stop 3524 would inhibit orprevent further rotation of the electrode system 3508. Such a system canprovide a predictable amount of rotational repositioning. The system3500 may comprise a stop 3516 (e.g., comprising a physical barrier) orother means for inhibiting or preventing accidental or unwanted movementof the knob 3512 and/or movement of the electrode system 3508.

FIG. 36A is a perspective view of an example of a catheter system 3600.The system 3600 comprises a proximal portion 3602 configured to remainout of the body of a subject and a distal portion 3604 configured to beinserted into vasculature of a subject. The distal portion 3604comprises an expandable structure 3620. The proximal portion comprises ahandle 3610 and an actuation mechanism 3612. The proximal portion 3602is coupled to the distal portion 3604 by a catheter shaft 3606. In someexamples, the system 3600 comprises a strain relief 3626 between thecatheter shaft 3606 and the expandable structure 3620. The proximalportion 3602 may comprise an adapter comprising a plurality of ports,for example the Y-adapter comprising a first Y-adapter port 3616 and asecond Y-adapter port 3618. The first Y-adapter port 3616 may be incommunication with a lumen configured to allow insertion of a guidewire3615 through the system 3600. The second Y-adapter port 3618 maycomprise an electronics connector 3619, which can be used to couple anelectrode matrix of the system 3600 to a stimulator system.

FIG. 36B is a perspective view of a portion of the catheter system 3600of FIG. 36A in a collapsed state. The illustrated portion includes partof the catheter shaft 3606, the strain relief 3626, and the expandablestructure 3620. The strain relief 3626 may be at least partially in alumen of the catheter shaft 3606. The expandable structure 3620 includesa plurality of splines 3622. Four of the splines 3622 comprise anelectrode array 3624 comprising four electrodes to form a 4×4 electrodematrix. The number of electrodes in the electrode matrix, electrodesizing, electrode spacing, etc. may be in accordance with other systemsdescribed herein. For example, in some examples, the expandablestructure 3620 comprises a mesh or membrane comprising electrodes thatis stretched across two or more of the splines 3622. The illustratedportion also includes an actuator wire 3628, which can be coupled to theactuator mechanism 3612 to cause expansion or retraction of theexpandable structure 3620. The actuator wire 3628 may be in a lumen ofthe catheter shaft 3606. A guidewire 3615 is also shown in the lumen ofthe actuator wire 3628. In some examples, the actuator wire 3628comprises a lumen capable of receiving a 0.018 inch guidewire 3615.

FIG. 36C is a side view of a portion of the catheter system 3600 of FIG.36A in an expanded state. Operation of the actuation mechanism 3612 cancause the expandable structure 3620 to expand and contract. For example,rotation and/or longitudinal movement of the actuation mechanism 3612can cause the actuator wire 3628 to proximally retract, which can pushthe splines 3622 radially outward. In some examples, the distal ends ofthe splines 3622 are coupled to a distal hub that is coupled to theactuator wire 3628, and the proximal ends of the splines 3622 arecoupled to a proximal hub that is coupled to the catheter shaft 3606. Inthe expanded state, the expandable structure 3620 comprises splines 3622that are spaced from each other generally parallel to a longitudinalaxis at a radially outward position of the splines 3622. The parallelorientation of the splines 3622 can provide circumferential spacing ofthe splines 3622, for example in contrast to singular splines or wiresthat may circumferentially bunch. In some examples, the splines 3622comprise wires having a diameter between about 0.006 inches (approx.0.15 mm) and about 0.015 inches (approx. 0.38 mm) (e.g., about 0.006inches (approx. 0.15 mm), about 0.008 inches (approx. 0.2 mm), about0.01 inches (approx. 0.25 mm), about 0.012 inches (approx. 0.3 mm),about 0.015 inches (approx. 0.38 mm), ranges between such values, etc.).A frame comprising openings between arms or splines can help withfixation of the expandable structure 3620. For example, vessel tissuecan deform such that some vessel tissue enters into the openings, whichcan provides a good fixation.

In some examples, the diameter 3621 of the expandable structure 3620 inthe expanded state is between about 15 mm and about 30 mm (e.g., about15 mm, about 20 mm, about 22 mm, about 24 mm, about 26 mm, about 28 mm,about 30 mm, ranges between such values, etc.). In some examples, thesplines 3622 may be self-expanding such that the actuation mechanism3612 or another mechanism (e.g., retraction of a sheath over the splines3622) allows the splines to self-expand from a compressed state fornavigation to a target site to an expanded state for treatment at thetarget site. In certain such examples, the diameter of the expandablestructure 3620 in the expanded state may be oversized to most theintended vasculature of most subjects to ensure vessel wall apposition.In some examples, the splines 3622 may be non-self-expanding such thatthe splines only expand upon operation of the actuation mechanism 3612.In some examples, the splines 3622 may be self-expanding, and theactuation mechanism 3612 may further expand the splines 3622, which mayprovide an adjustable expandable structure 3620 diameter usable for arange of vessel sizes, wall apposition forces, etc. Examples in whichthe expandable structure 3620 does not appose the wall in the event ofan error could be advantageous for safety, for example as described withrespect to the system 2200. In some examples, the wires are not fixeddistally (e.g., to a distal hub), which can allow each wire to moveindependently, which may accommodate curvature at a deployment site.Upon expansion of the expandable structure 3620, the electrodes of theelectrode matrix may be selectively activated for testing nerve capture,calibration, and/or therapy, for example as described herein.

FIG. 36D schematically illustrates a side view of an example of anexpandable structure 3620. The expandable structure 3620 comprises eightsplines 3622 extending from a proximal hub 3607 to a distal hub 3608.The splines 3622 are grouped in pairs that run generally parallel toeach other. Pairs of the splines 3622 may be different wires or the samewire (e.g., bent at the proximal end or the distal end), for example asdescribed herein. The splines 3622 extend laterally and only outwardlyfrom the proximal hub 3607 at a first angle to the longitudinal axis3671, or parallel to the longitudinal axis 3671 and then bend to formthe first angle after a short length. The splines 3622 continue at thatangle for a first length 3675. In some examples, an angle between thelongitudinal axis 3671 and the first length 3675 is between about 10°and about 60° (e.g., about 10°, about 20°, about 30°, about 40°, about50°, about 60°, ranges between such values, etc.).

After the first length 3675, the splines 3622 of each pair of parallelsplines circumferentially diverge at second angles from an axis alignedwith the splines along the first length 3675, coming out of plane withthe longitudinal axis 3671. The second angles may be the same ordifferent. After a short length, the splines 3622 bend again at thirdangles relative to the axis of the first length 3675 to return thesplines 3622 to being parallel with each other. The third angles may bethe same or different. In some examples, a difference between the secondangles and a difference between the third angles are complementary. Thesplines 3622 are parallel for a second length 3676 at a fourth anglewith the longitudinal axis 3671, the fourth angle being about 0°. Insome examples, an angle between the first length 3675 and the secondlength 3676 is between about 120° and about 170° (e.g., about 120°,about 130°, about 140°, about 150°, about 160°, about 170°, rangesbetween such values, etc.).

After the second length 3676, the splines 3622 bend at fifth anglescoming out of plane with the longitudinal axis 3671 for a short distanceuntil the splines 3622 converge. The fifth angles may be the same ordifferent. In some examples, one or both of the fifth angles is the sameas one or both of the third angles. After the splines 3622 converge, thesplines 3622 bend at seventh angles, which return the splines 3622 tobeing parallel with each other and coming into plane with thelongitudinal axis 3671 for a third length 3677, still at the fifth anglewith respect to the longitudinal axis 3671. In some examples, an anglebetween the longitudinal axis 3671 and the third length 3677 is betweenabout 10° and about 60° (e.g., about 10°, about 20°, about 30°, about40°, about 50°, about 60°, ranges between such values, etc.). In someexamples, an angle between the third length 3677 and the second length3676 is between about 120° and about 170° (e.g., about 120°, about 130°,about 140°, about 150°, about 160°, about 170°, ranges between suchvalues, etc.). The first length 3665 may be the same as or differentfrom the third length 3667. After the third length 3677, the splines3622 bend into the distal hub 3608 at the fifth angle or bend to extendinto the distal hub 3608 parallel to the longitudinal axis 3671.

The angles described herein may refer to the shape of the expandablestructure 3620 in the absence of forces. Forces applied by a sheathand/or actuator wire 3628 may increase or decrease the angles. Forexample, restraint of the expandable structure 3620 in a sheath mayreduce the angles of the first length 3675 and the third length 3677relative to the longitudinal axis 3671. For another example,longitudinal extension of the distal hub 3608 relative to the proximalhub 3607 (e.g., by distally advancing the actuator wire 3628) may reducethe angles of the first length 3675 and the third length 3677 relativeto the longitudinal axis 3671. For yet another example, longitudinalretraction of the distal hub 3608 relative to the proximal hub 3607(e.g., by proximally retracting the actuator wire 3628) may increase theangles of the first length 3675 and the third length 3677 relative tothe longitudinal axis 3671.

The area created by the pairs of splines 3622 diverging, being parallel,and then converging, may be a cell. The splines 3622 may compriseelectrodes along at least the second length 3672. This pattern may beproduced using any number of splines 3622. Other bend patterns are alsopossible. For example, the splines 3622 may bend to become parallel withthe longitudinal axis 3671 before diverging and/or remain parallel withthe longitudinal axis 3671 until converging and/or may converge and/ordiverge at a non-parallel angle to the first length 3675 and the secondlength 3677. For another example, the splines 3622 may diverge along thefirst length 3675 and/or converge along the third length 3677. For yetanother example, a single wire may be bent back and forth to form thesplines 3622. For still another example, the bends may be more gentlycurved than angular. The elongated contact between the splines 3622along the second length 3676 and the vessel walls can inhibit or preventwobble of the longitudinal axis 3671 of the expandable structure 3620.In some examples, the expandable structure 3620 comprises parallelportions for splines 3622 that comprise electrodes, but splines 3622that do not comprise electrodes, for example splines 3622 that are usedfor vessel wall apposition, may comprise parallel wires, non-parallelwires, wires with other shapes, wires with different diameters,different numbers of wires (e.g., more or fewer), etc. In certain suchexamples, the expandable structure 3620 may be radially and/orcircumferentially asymmetrical.

FIG. 36E schematically illustrates a side view of another example of anexpandable structure 3630. The portions of the splines 3632 of theexpandable structure 3630 comprising electrodes (e.g., as shown in FIG.36C) are radially inward from an outer diameter in the expanded state.The intersection of the recessed portions and the outer diameter cancreate anchor points 3634, which can help to secure the position of theexpandable structure 3630. In some examples, an expandable structure3620 may take the shape of the expandable structure 3630.

FIG. 36F schematically illustrates a side view of still another exampleof an expandable structure 3640. The portions of the splines 3642 of theexpandable structure 3640 comprising electrodes (e.g., as shown in FIG.36C) protrude radially outward or are crowned in the expanded state. Insome examples, an expandable structure 3640 may take the shape of theexpandable structure 3620, for example because the generally straightvessel wall may straighten the portions of the splines 3642. A crownedexpandable structure 3640 may counteract forces on an expandablestructure 3620 that may result in the shape of the expandable structure3630 in a vessel, which may increase apposition area and/or reducelongitudinal wobble.

FIG. 36G schematically illustrates a perspective view of yet anotherexample of an expandable structure 3650. The expandable structures 3620,3630, 3640 are illustrated as having splines 3622, 3632, 3642 that areparallel until diverging to form the parallel portions. The expandablestructure 3650 comprises twisted wires 3652 rather than parallel wires,which can make the expandable structure 3650 stiffer while stillproviding some amount of movement as the wires are able to slightlyslide along and around each other. A stiffer expandable structure 3650may help with circumferential spacing of the parallel portions andelectrodes of the electrode matrix. In some examples, wires of theexpandable structure 3650 or the expandable structures 3620, 3630, 3640can be coupled (e.g., using a coupling structure), crimped, welded,soldered, adhered, combinations thereof, and the like, which can also oralternatively increase stiffness.

FIG. 36H schematically illustrates an example of an expandable structurepattern. The pattern is also illustrated in the expandable structures3620, 3630, 3640, and includes parallel portions having proximalstarting and distal ending points that are generally circumferentiallyaligned. Circumferential alignment may reduce manufacturing complexity,for example because the expandable structure 3620 is symmetrical so thesame tooling and setup may be used to shape each wire. Circumferentialalignment may provide electrode matrix flexibility, for example if eachof the splines comprises the same electrode array such that anyrotational position is acceptable.

FIG. 36I schematically illustrates another example of an expandablestructure pattern. The middle parallel portions have proximal startingand distal ending points that are shifted distally from the proximalstarting and distal ending points, respectively, of the top and bottomparallel portions. Staggering the starting and/or ending points canallow the splines to nest in a collapsed state, which can reduce systemdiameter. Staggering the starting and/or ending points can reduce thechances that an electrode may snag during expansion and/or collapse ofthe expandable structure.

FIG. 36J schematically illustrates another example of an expandablestructure pattern. The middle parallel portions have proximal startingpoints that are shifted proximally and distal ending points that areshifted distally from the proximal starting and distal ending points,respectively, of the top and bottom parallel portions. Staggering thestarting and/or ending points can allow the splines to nest in acollapsed state, which can reduce system diameter. Staggering thestarting and/or ending points can reduce the chances that an electrodemay snag during expansion and/or collapse of the expandable structure.

FIG. 36K schematically illustrates another example of an expandablestructure pattern. The wires includes parallel portions as in theexpandable structures 3620, 3630, 3640, and the portions of the wiresproximal and distal to the parallel portions do not circumferentiallyconverge for each set of parallel portions. Wires that do not convergeor wires that converge less or partially (e.g., at one end of each setof parallel portions) can reduce forces (e.g., rotational or twistingforces) that may otherwise cause uneven spacing of the parallel portionsin an expanded state.

FIG. 36L schematically illustrates another example of an expandablestructure pattern. The parallel portions comprise a third non-divergingspline between the diverging parallel portions. In examples in whicheach of the splines includes electrodes, a third spline can increase thenumber of rows in an electrode matrix and/or provide more flexibility inelectrode positioning. More or fewer wires or splines are also possible.Some or all of the wires or splines may include electrodes and/or may becoupled to a membrane or mesh comprising electrodes.

FIG. 36M schematically illustrates another example of an expandablestructure pattern. As opposed to comprising a plurality of wires, thesplines comprise flat surfaces of a cut hypotube. In some examples, aplurality of electrodes is positioned on an outer side of one or moresplines. A wide variety of cut patterns are possible. For example,splines comprising electrodes may be shaped to correspond to theelectrode shapes and/or pattern. In some examples, the splines maycomprise flat wires (e.g., having a rectangular cross-section). In someexamples, the splines may comprise U-shaped wires (e.g., as describedherein.

FIG. 36N schematically illustrates an example of an expandablestructure. The expandable structure comprises a mesh 3660 coupled to thesplines. The mesh 3660 may comprise an electrode matrix in accordancewith the disclosure herein. In some examples, a first circumferentialedge of the mesh 3660 may be coupled to a first spline and a secondcircumferential edge of the mesh 3660 may be coupled to a second splinesuch that the remainder of the mesh can slide with respect to othersplines.

FIG. 36O schematically illustrates an example of an expandable structurepattern. The splines comprise a sinusoidal or wave or undulating orzig-sag shape. The undulating wires may provide more flexibility inelectrode positioning. For example, electrodes may be placed at peaks,troughs, and/or rising or falling portions. The undulating wires mayprovide better wall apposition than parallel portions due to moresurface area contact with the vessel wall.

FIG. 36P schematically illustrates a side view of an example of anexpandable structure 3660. FIG. 36Q is a proximal end view of theexpandable structure 3660 of FIG. 36P. The expandable structure 3660comprises ten splines 3662 extending from a proximal hub 3663 to adistal hub 3664. The splines 3662 are grouped in pairs that rungenerally parallel to each other. Pairs of the splines 3662 may bedifferent wires or the same wire (e.g., bent at the proximal end or thedistal end), for example as described herein. The splines 3622 may eachhave a proximal starting point and distal ending point that are notcircumferentially aligned. The splines 3662 extend from the proximal hub3663 at a first angle to the longitudinal axis 3661, or straight andthen bend to the first angle after a short length. The splinessimultaneously extend in a circumferential direction at a second anglerelative to a circumferential origin. The splines 3662 continue at thoseangles for a first length 3665. After the first length 3665, half of thesplines 3662, one from each pair of parallel splines 3662, bends in acircumferential direction at a third angle greater than the secondangle, and the other half of the splines 3662, the other from each pairof parallel splines 3662, bends at a fourth angle opposite the secondangle. These bends cause the pairs of splines 3662 to circumferentiallydiverge.

After a short length, the splines 3622 bend again, at a fifth angle anda sixth angle, so that the pairs of splines 3662 are parallel to eachother, at a seventh angle 3668 relative to the longitudinal axis 3661,for a second length 3666. The second length 3666 may be the same as ordifferent than (e.g., greater than) the first length 3665. The seventhangle 3668 may be the same as or different than the first angle. Theseventh angle 3668 may be between about 5° and about 60° (e.g., about5°, about 10°, about 15°, about 20°, about 25°, about 30°, about 35°,about 40°, about 45°, about 50°, about 55°, about 60°, ranges betweensuch values, etc.). After the second length 3666, the splines 3662 againbend in opposite circumferential directions, at an eight angle and anninth angle opposite to the seventh angle, to circumferentially convergeat a tenth angle relative to the longitudinal axis 3661. The areascreated by the pairs of splines 3662 diverging, being parallel, and thenconverging, may be a cell. The splines 3662 may comprise electrodesalong at least the second length 3666. The tenth angle may be the sameor different as the first angle. After a short length, the splines 3662bend again, at an eleventh angle and a twelfth angle, so that the pairsof splines 3662 are again parallel to each other, at the tenth anglerelative to the longitudinal axis 3661 and a thirteenth angle relativeto the circumferential origin, for a third length 3667. The third length3667 may be the same as or different than the first length 3665. Thesecond length 3666 may be the same as or different than (e.g., lessthan) the second length 3666. In the example illustrated in FIG. 36P,the first length 3665 is about the same as the third length 3667, andthe second length 3666 is greater than each of the first length 3665 andthe third length 3667. The thirteenth angle may be the same as ordifferent than the seventh angle. The thirteenth angle may be the sameas or different than the second angle. The splines 3662 extend intodistal hub 3664 at the tenth angle relative to the longitudinal axis3661 and the thirteenth angle relative to the circumferential origin, orbend to extend straight into the distal hub 3664.

The starting proximal point and distal ending point for each spline 3622may be circumferentially offset, for example depending on the bendangles and lengths. This pattern may be produced using any number ofsplines 3662. Splines 3662 at an angle to the longitudinal axis 3661 mayprovide better wall apposition than splines that extend parallel to thelongitudinal axis, for example due to increased surface area contactwith the vessel wall. Although the expandable structure 3660 may beconsidered an angled, 5-pair version of the expandable structure 3620,for example, any of the expandable structures described herein may beangled as appropriate. In some examples, the splines 3662 may be shapeset to be angled. In some examples, the splines 3662 may be angledduring use, for example by rotating the distal hub 3664 relative to theproximal hub 3663.

Combinations of the expandable structure patterns described herein andother expandable structure patterns are also possible. For example, anexpandable structure may comprise longitudinal offset and three wires.For another example, an expandable structure may comprise longitudinaloffset and undulating wires. In some examples, an anchor (e.g., barb)may be integrated with splines of an expandable structure.

FIG. 37A is a perspective view of an example of catheter system 3700.The catheter system 3700 may share at least some similar features withthe catheter system 3600 and/or other catheter systems described herein.The system 3700 comprises a proximal portion 3702 configured to remainout of the body of a subject and a distal portion 3704 configured to beinserted into vasculature of a subject. The distal portion 3704comprises an expandable structure 3720. The proximal portion comprises ahandle 3710. A catheter shaft assembly 3706 extends from the handle 3710to the proximal end of the expandable structure 3720. An actuation tube3728 extends from the handle 3710 through the catheter shaft assembly3706 to the distal end of the expandable structure 3720. The proximalend 3702 further comprises an electrical socket 3799, which isconfigured to connect to an electrical plug of a neurostimulator (e.g.,radiofrequency generator or other appropriate source depending on thestimulation or ablation modality).

FIG. 37B schematically illustrates a side view of expandable structure3720 and FIG. 37C shows a proximal end view of expandable structure3720. The expandable structure 3720 includes a plurality of splines 3722extending from a proximal hub 3740 to a distal hub 3750. Some splines3722 of the expandable structure 3720 may include electrodes 3724configured to stimulate a target nerve. Some of the splines 3722 may bedevoid of, free from, or not include electrodes 3724. In some examples,the expandable structure 3720 includes ten splines 3722, of which fourcircumferentially adjacent splines 3722 each comprise five electrodes3724. The splines 3722 may comprise proximal segments, intermediatesegments, and distal segments. The intermediate segments may beconfigured to extend radially outward when the expandable structure 3720is in a self-expanded state. The proximal segment of a spline 3722 mayform a first angle with the intermediate segment and the distal segmentmay form a second angle with the intermediate segment. In some examples,the proximal segment and distal segment may be straight and theintermediate segment may be convex, bending radially outward. In someexamples, the proximal segment and distal segment may be straight andthe intermediate segment may be concave, bending radially inward. Insome examples, the proximal segment, intermediate segment, and distalsegment may all be straight. Splines 3722 which comprise electrodes 3724may comprise proximal segments and distal segments devoid of electrodes3724. The splines 3722 may further comprise proximal transitionalsegments, joining the proximal segments and intermediate segments, anddistal transitional segments, joining the intermediate segments anddistal segments.

The splines 3722 comprising electrodes 3724 may be configured to extendoutwardly on one side of a plane crossing a longitudinal axis of theexpandable structure 3720. The splines 3722 not comprising electrodes3724 may be configured to extend outwardly on a second side of the planeopposite the one side. For example, the splines 3722 not comprisingelectrodes 3724 illustrated in FIG. 37C could be less circumferentiallyspaced to be on the same side of a plane crossing the longitudinal axisat the center of the expandable structure 3720. The splines 3722comprising electrodes 3724 may circumferentially occupy less than 180°on the one side. For example, the splines 3722 comprising electrodes3724 may circumferentially occupy about 30° to about 170° (e.g., about30°, about 45°, about 60°, about 90°, about 100°, about 110°, about120°, about 150°, about 170°, ranges between such values, etc.). Thefour splines 3722 comprising electrodes 3724 illustrated in FIG. 37Ccircumferentially occupy about 110°.

Other numbers of splines 3722 comprising electrodes 3724 are alsopossible. For example, all of the splines 3722 or a subset of thesplines 3722 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 of the splines3722) may comprise an electrode 3724. In examples comprising more than10 splines, more than 10 splines may comprise an electrode. All of thesplines 3722 or a percentage of the splines 3722 (e.g., 10%, 20%, 30%,40%, 50%, 60%, 70%, 80%, 90%, or 100% of the splines 3722) may comprisean electrode 3724. The splines 3722 that comprise an electrode 3724 maybe circumferentially adjacent or have one or more non-electrode splines3722 therebetween.

The splines 3722 may comprise between one electrode 3724 and twentyelectrodes 3724 (e.g., 1 electrode, 2 electrodes, 3 electrodes, 4electrodes, 5 electrodes, 6 electrodes, 7 electrodes, 8 electrodes, 9electrodes, 10 electrodes, 15 electrodes, 20 electrodes, ranges betweensuch values, etc.). More electrodes 3724 can provide more stimulationoptions and/or more targeted nerve capture. Fewer electrodes 3724 canreduce the number of electrical connectors, which can reduce deviceprofile and/or reduce valuable device volume taken by electricalconnectors.

FIG. 37D is a perspective view of a wire bent to form a spline pair3727. A single wire may be bent at a bend 3725 to form a spline pair3727 comprising a first spline 3722A from a first portion of the wireand a second spline 3722B from a second portion of the wire. The bend3725 may be positioned at the proximal end of the spline pair 3727, suchthat a proximal-facing end of the spline pair 3727 is an atraumatic bendas opposed to possibly traumatic wire ends. The bend 3725 may bepositioned at the distal end of the spline pair 3727. The spline pair3727 may be formed with two or more individual wires positioned in thesame configuration, for example coupled by welding, soldering, etc. Thesplines 3722A, 3722B may each comprise a different wire. The wires maybe coupled, for example at a proximal end, or not coupled. One or bothends of the wires may be bent to be atraumatic. The spline pair 3727 maybe shaped with two generally parallel splines 3722 which run alongsideeach other at their proximal and distal ends (e.g., along proximal anddistal segments) but are separated by a greater distance along a centralportion (e.g., an intermediate segment). As best seen in FIG. 37C, thesplines 3722 circumferentially diverge at the beginning and end of acentral portion of the spline 3722 (e.g., along proximal transitionalsegments and distal transitional segments) as they continue to extendradially outward. The convergence and divergence of the splines 3722forms two short lengths during which the splines 3722 in a spline pair3727 are not parallel. The splines 3722 of a spline pair 3727 runparallel within their central portions to form a generally hexagonalshape. The splines 3722 may share features with any of the patterns orconfigurations of expandable structures disclosed herein or variationsthereof. As non-limiting examples, the central portions of the splines3722 may be substantially parallel to the longitudinal axis of theexpandable structure 3720, for example as shown in FIG. 36H, curveradially inward, for example as shown in FIG. 36E, radially outward, forexample as shown in FIG. 36F, and/or have other configurations.

Some splines 3722 of the expandable structure 3720 may not include orlack or be devoid of or be free of electrodes 3724. After inserting thesplines 3722 without electrodes 3724 through the proximal hub 3740, thesplines 3722 may be wrapped with heat shrink tubing 3721, for examplealong their parallel and adjacent proximal and distal portions. The heatshrink tubing 3721 is then shrunk by heating. The heat shrink tubing3721 may comprise, for example, polyethylene terephthalate (PET) oranother suitable material. The heat shrink tubing 3721 can help inhibitrotation of the wrapped portions of the splines 3722 of a spline pair3727 relative to each other. If the expandable structure 3720 isretracted through the pulmonary valve in an expanded state, the heatshrink tubing 3721 along the proximal portion of the splines 3722 mayprovide a more favorable proximally-facing surface than the splines 3722for interaction with the valve tissue.

The wires forming the splines 3722 may be formed from a shape memoryalloy such as Nitinol. In such cases, the wires are heated andprogrammed into a desired memory shape, such as the configurationdepicted in FIG. 37D, then rapidly cooled. The wires may then bedeformed as needed and inserted through the spline lumens 3745 and willreturn to their predetermined memory shape upon heating above atransition temperature. Once the wire is threaded through two adjacentspline lumens 3745 and returned to its programmed conformation,including the spline bend 3725 in the wire, the spline pair 3727 may bepulled distally until the spline bend snaps into place within a recess3747 behind a proximal hub step 3748 (FIG. 37G).

FIG. 37E is a perspective view of a spline pair 3727. The spline pair3727 comprises five electrodes 3724 positioned across the centralportion of each splines 3722A, 3722B. The two splines 3722A, 3722B of asingle spline pair 3727 may each comprise an electrode 3724, may each bedevoid of electrodes 3724, or one of the splines 3722A, 3722B maycomprise an electrode 3724 while the other of the splines 3722A, 3722Bis devoid of electrodes.

FIG. 37F is an expanded view of the distal end of the spline pair 3727of FIG. 37E. The splines 3722 comprising an electrode 3724 may be atleast partially covered by a lining 3729, for example not at theproximal end and/or distal end. The lining 3729 may comprise PTFE. Inexamples in which the inner surfaces of the electrodes 3724 are notinsulated, the lining 3729 may electrically insulate the splines 3722from the electrodes 3724, which can inhibit cross-talk, activation ofunintended electrodes, inefficient operation due to electrical leakage,etc. In examples in which the inner surfaces of the electrodes 3724 areinsulated or other circumstances, the lining 3729 may be omitted. Thesplines 3722 not comprising an electrode 3724 may be free of a lining3729, for example to provide better vessel wall apposition that is notprone to sliding. After inserting the splines 3722 through the proximalhub 3740, which may be before or after lining, lined spline wires may bewrapped with a spline tube 3723 that joins the two splines 3722A, 3722Bof a spline pair 3727 at their proximal and distal ends. The spline tube3723 may comprise two adjacent, yet, distinct lumens for each spline3722 or it may comprise a single (e.g., oblong) lumen at its proximaland distal ends for receiving both splines. The spline tube 3723 maysplit at the proximal and distal points where the splines 3722A, 3722Bdiverge and cover each spline 3722A, 3722B individually along itscentral portion, such that the spline tube 3723 has two Y-shaped ends.Being spaced at the central portion of a spline pair 3727 may reduce therisk of thrombosis and/or provide better wall apposition by allowing thesplines 3722 to abut the wall at circumferential points. The spline tube3723 may span the expanse between the central portions of the splines3722, which may provide a wider variety of electrode 3724 configurations(e.g., as described with respect to FIG. 4C) and/or provide better wallapposition by providing more apposition surface area. A plurality ofspline tubes 3723 may be used, for example, one spline tube 3723 foreach spline 3722. Spline tubes 3723 may optionally be coupled, forexample at proximal and distal portions of a spline pair 3727. Splinetubes 3723 may be sized to be touching but not coupled. The spline tube3723 may inhibit rotation of splines 3722A, 3722B of a spline pair 3727relative to each other.

The individual electrodes 3724 may be generally cylindrical surroundingthe circumference of central portions of the splines 3722. Other typesand configurations of electrodes 3724 are also possible. For example,the electrodes 3724 may extend only partially around the circumferenceof the splines 3722 such that they face the outer diameter of theexpandable structure 3720 (e.g., as described with respect to theelectrode 4403).

The expandable structure 3720 may comprise five spline pairs 3727 spacedabout the circumference of the expandable structure. The spline pairs3727 may be evenly circumferentially spaced (e.g., as shown in FIG.37C). Some of the spline pairs 3727 may be circumferentially clustered.For example, spline pairs 3727 comprising electrodes 3724 may be on afirst side of a plane intersecting the longitudinal axis and splinepairs without electrodes 3724 may be on a second side of the planeopposite the first side. Two circumferentially adjacent spline pairs3727 may each comprise a set of electrodes 3724, such as five electrodes3724 per spline 3722, to form a 4 x 5 array of twenty electrodes 3724.

FIGS. 37Fi-37Fiii illustrate an example of electrical movement ofelectrodes. The expandable structure 3720, or other expandable membersdescribed herein, is expanded in a vessel. The electrodes may beselectively activated, for example as described herein, to determine acombination that stimulates the target nerve. In FIG. 37Fi, twoelectrodes in the first column have been found to capture a target nervewhen activated. After some duration of treatment, stimulation of thetarget nerve may not be as effective as during the original selection.One option would be to contract, reposition, and reexpand the expandablestructure 3720, and then repeat the selective activation process.Another non-mutually exclusive option is to electrically move theexpandable structure 3720 to better capture the target nerve. In FIG.37Fii, two electrodes in the fourth column have been found to capturethe target nerve when activated. Changing the stimulation from theelectrodes in the first column to the electrodes in the fourth columneffectively moves or longitudinally shifts the expandable structure 3720by the distance 3701. In FIG. 37Fiii, two electrodes in the first columnbut in the second and third rows have been found to capture the targetnerve when activated. Changing the stimulation to these electrodeseffectively circumferentially rotates the expandable structure 3720 bythe distance 3703. Combinations of effective longitudinal movement andcircumferential rotation are also possible. Although illustrated asbipolar operation in which two electrodes have opposite charges,monopolar operation (e.g., stimulation of one or more electrodes withthe same charge in combination with a return electrode that is not anelectrode of the electrode array (e.g., a chest pad, on a proximalportion of the catheter system 3700, on a separate catheter, etc.) isalso possible. Although illustrated as simple bipolar operation for easeof explanation, guarded bipolar operation and other techniques are alsocompatible with electrical movement. Factors that may affect theprecision with which an electrode array can capture a target nerve mayinclude the total number of electrodes 3724, the span and shape of anelectrode array, the proportioning of electrodes 3724 on individualsplines 3722, the spacing of electrodes 3724 across the lengths of thesplines 3722, and the circumferential spacing of the splines 3722, etc.An electrode array configured to allow electrical movement mayadvantageously reduce or eliminate physical or mechanical repositioningthe expandable structure 3720, which could include contracting, moving,and reexpanding the expandable structure 3720. Physical movement cancause adverse events such as ischemic stroke (e.g., by causing debris tofloat loose or promoting thrombosis), damage to the vessel wall (e.g.,promoting stenosis), etc. Physical movement can be time consuming,during which the subject may not be being treated.

Referring again to FIG. 37B, the expandable structure 3720 comprises aproximal hub 3740 and distal hub 3750 from which the splines 3722extend. The proximal hub 3740 may comprise stainless steel or anothersuitable material. The distal hub 3750 may comprise stainless steel oranother suitable material. The proximal hub 3740 and the distal hub 3750may comprise the same material or different materials.

FIG. 37G is a perspective view of an example of a proximal hub 3740 ofan expandable structure (e.g., the expandable structure 3720). FIG. 37Hschematically illustrates a side cross-sectional view of the proximalhub 3740 of FIG. 37G. The proximal hub 3740 may comprise a biocompatiblematerial such as, for example, stainless steel, nitinol, plastic, etc.The proximal hub 3740 may comprise a proximal portion 3741 and a distalportion 3742. The distal portion 3742 has a larger diameter than theproximal portion 3741 and may taper at its distal end to form apartially rounded surface 3749. A central lumen 3743 extends throughboth the proximal portion 3741 and the distal portion 3742, providing achannel from the proximal end of the proximal hub 3740 to the distal endof the proximal hub 3740 through which an actuation tube 3728 mayslidingly extend. Although illustrated as having a circularcross-section, the central lumen 3743 may have other cross-sectionalshapes (e.g., oval, arcuate, polygonal, etc.). The central lumen 3743may include a lubricious coating or liner (e.g., comprising PTFE).

The proximal portion 3741 may be radially inward of the distal portion3742. In some examples, a difference in diameter or outer dimension ofthe proximal portion 3741 and the distal portion 3742 may beapproximately the thickness of a hinge 3726, which can allow theproximal hub 3740 to be coupled to a hinge 3726 while maintaining auniform outer sheath 3711 (FIG. 37O) diameter if the outer sheath 3711overlaps the distal portion 3742. In some examples, a difference indiameter or outer dimension of the proximal portion 3741 and the distalportion 3742 may be approximately the thickness of a hinge 3726 plus thethickness of an outer sheath 3711, which can allow the proximal hub 3740to be coupled to a hinge 3726 while maintaining a uniform diameter ifthe outer sheath 3711 abuts the distal portion 3742. Other differencesmay be appropriate for other types of catheter shafts, for example notincluding a hinge 3711.

A plurality of peripheral lumens 3744 extends through both the proximalportion 3741 and distal portion 3742, providing a plurality ofperipheral channels from the proximal end of the proximal hub 3740 tothe distal end of proximal hub 3740 through which electrical connectorsmay extend and/or through which fluid may flow. The peripheral lumens3744 may be radially outward of the central lumen 3743. The peripherallumens 3744 may have a smaller diameter than the central lumen 3743. Theperipheral lumens 3744 may each have the same diameter or at least oneof the peripheral lumens 3744 may have a different diameter. Althoughillustrated as having a circular cross-section, the peripheral lumens3744 may have other cross-sectional shapes (e.g., oval, arcuate,polygonal, etc.). The peripheral lumens 3744 may each have the sameshape or at least one of the peripheral lumens 374 may have a differentshape. For example, peripheral lumens 3744 configured for an electricalconnector to extend therethorugh may have one diameter or shape andperipheral lumens 3744 configured to deliver fluid may have anotherdiameter or shape. Although the proximal hub 3740 is illustrated ashaving five peripheral lumens 3744, other quantities of peripherallumens 3744 are also possible. For example, the proximal hub 3740 mayinclude at least one peripheral lumen 3744 per spline pair 3727, atleast one peripheral lumen 3744 per spline 3722, at least one peripherallumen 3744 per spline 3722 comprising an electrode, at least oneperipheral lumen 3744 per spline pair 3727 comprising an electrode, atleast one peripheral lumen 3744 per electrical connector, etc. Althoughthe proximal hub 3740 is illustrated as having five peripheral lumens3744 equally spaced about the circumference of the proximal hub 3740,other arrangements of the peripheral lumens 3744 are also possible. Someperipheral lumens 3744 may be circumferentially bunched or grouped orclustered. For example, peripheral lumens 3744 configured for anelectrical connector to extend therethrough may be circumferentiallyclustered and peripheral lumens 3744 configured to deliver fluid may besubstantially equally circumferentially spaced about the remainder ofthe proximal hub 3740. A proximal hub 3740 comprising peripheral lumens3744 that each have the same size, shape, and spacing may providemanufacturing flexibility and/or adaptability to a variety of designs. Aproximal hub 3740 comprising at least one peripheral lumen 3744 having adifferent size, shape, and/or spacing may provide enhanced performancefor a type of design.

The distal portion 3742 of the proximal hub 3740 may comprise splinelumens 3745. One or more splines 3722 may be positioned in each splinelumen 3745. In an example method of manufacture, a wire may be bent, forexample as shown in FIG. 37D. The free ends of the wire may be insertedinto the proximal ends of the spline lumens 3745 and then advanceddistally until the bend 3725 contacts or is proximate to the proximalend of the distal portion 3742 of the proximal hub 3740. The bend 3725in each spline pair 3727 can inhibit or prevent the spline pair 3727from sliding distally because it contacts the proximal end of the distalportion 3742 of the proximal hub 3740.

The proximal portion 3741 may include recesses 3747 configured toaccommodate or receive portions of splines 3722 extending proximal tothe proximal end of the distal portion 3742 of the proximal hub 3740.The portions of the splines 3722 may comprise the bends 3725. Theportions of the splines 3722 may comprise the free ends of the splines3722, which may optionally be bent, for example to an atraumatic shape.If the recesses 3747 are flattened portions of an otherwise arcuateproximal portion 3741, the segment between the recesses 3747 and theradially outward surface may form steps 3748. The proximal portion 3740may comprise one recess 3747 and one step 3748 per spline pair 3727. Theproximal portion 3740 may comprise one recess 3747 and one step 3748 pertwo splines 3722, whether or not in a spline pair 3727. The proximalportion 3740 may comprise one recess 3747 and one step 3748 per spline3722. The proximal portion 3740 may comprise one arcuate recess 3747around or substantially around the circumference of the proximal portion3740. The proximal portion 3740 may comprise one or more arcuaterecesses 3747 for splines 3722 comprising an electrode 3724 and one ormore recesses 3747 for splines 3722 lacking an electrode 3724.

The steps 3748 may limit the proximal motion of the proximal ends of thesplines 3722. In implementations comprising a bend 3725, if the splines3722 came out of the recesses 3747, then the surfaces that mightinteract with a vessel wall during retraction of an expandable structure3720 comprising the splines 3722 and proximal hub 3740 would beatraumatic, and thus may not be prone to puncturing or otherwiseadversely affecting the vessel. If the distal ends of the splines 3722were straight wires and came out of the distal hub 3750, then thesurfaces that might interact with a vessel wall during proximalretraction would be facing distally, the direction opposite retraction,and thus may not be prone to puncturing or otherwise adversely affectingthe vessel. If the splines 3722 of the expandable structure 3720 have aportion that is bent radially outward, then the proximal and distal endsof the splines 3722 may be biased to be radially inward of an outwardsurface, and thus may not be prone to puncturing or otherwise adverselyaffecting the vessel.

The splines 3722 may be slidingly engaged with the spline lumens 3745.Upon proximal retraction of an actuation tube 3728, the steps 3748 mayprovide a counter force against the proximal ends of the splines 3722,forcing the splines 3722 to bend radially outward. The radially outwardconfiguration may be different, for example, than an expandedconfiguration provided by shape memory. The splines 3722 may be fixablycoupled to the spline lumens 3745. In certain such implementations, theinteraction between the splines 3722 and the spline lumens 3745,independent of recesses 3747, steps 3748, and/or the proximal end of thedistal section 3742 of the proximal hub 3740, can inhibit proximal anddistal motion of the splines 3722 relative to the hub 3740. In someexamples, friction between the splines 3722 and the spline lumens 3745may provide additional or alternative counter force. The bends 3725 inthe spline pairs 3727 form atraumatic proximal ends, which can be lessdangerous to vasculature in a device failure scenario that results inthe proximal ends of the splines 3722 coming free or misaligned suchthat they inadvertently contact the walls of the blood vessel. Thespline pairs 3727 may be formed from individual wires or wirescomprising a bend at their distal ends. In certain such examples, thesplines 3722 may comprise a proximal bend or loop, the splines 3722 maybe fixably coupled to the spline lumens 3745, and/or the splines lumens3755 may comprise channels that are closed off at their proximal ends.The distal end of the distal portion 3742 of the proximal hub 3740 maybe tapered such that the distal end of spline lumens 3745 open at anangle to a rounded surface 3749. The angled open ends of the splinelumens 3745 at their distal ends may allow the splines 3722 to moreeasily bend radially outward, which may reduce stress on the wire whenadopting an expanded configuration.

FIG. 37I is a perspective view of a distal end of the proximal hub 3740of FIG. 37G. The wires or leads or conductors 3712 connecting theelectrodes 3724 to the electrical socket 3799 may extend through theperipheral lumens 3744 of the proximal hub 3740. As illustrated in FIG.37I, the conductors 3712 may be apportioned between the peripherallumens 3744 such that the conductors 3712 for all of the electrodes ofone or more splines 3722 extend through the same peripheral lumen 3744.For example, if the expandable structure 3720 comprises two adjacentspline pairs 3727 each comprising five electrodes 3724, the fiveconductors 3712A connected to the electrodes 3724 of a first spline 3722may extend through a first peripheral lumen 3744A, the five conductors3712B connected to the electrodes 3724 of a second spline 3722 in aspline pair 3727 with the first spline 3722 may extend through a secondperipheral lumen 3744B, the five conductors 3712C connected to theelectrodes 3724 of a third spline 3722 may extend through the secondperipheral lumen 3744B, and the five conductors 3712D connected to theelectrodes 3724 of a fourth spline 3722 in a spline pair 3727 with thethird spline 3722 may extend through a third peripheral lumen 3744C. Afourth peripheral lumen 3744D and a fifth peripheral lumen 3744E may befree of conductors 3712. Other distributions of conductors 3712 inperipheral lumens 3744 are also possible. For another example, all ofthe conductors 3712 may extend through one peripheral lumen 3744. Foryet another example, all of the conductors 3712 for each spline 3722 mayextend through one peripheral lumen 3744 that is different for eachspline 3722. For still another example, all of the conductors 3712 fortwo splines 3722 (e.g., in a spline pair 3727) may extend through oneperipheral lumen 3744. A peripheral lumen 3744 free from conductors 3712may be circumferentially between two peripheral lumens 3744 withconductors 3712 extending therethrough. Fluid flow through a peripherallumen 3744 may be inversely proportional to the number of conductors3712 occupying the peripheral lumen 3744, such that more fluid flowsthrough peripheral lumens 3744 with fewer conductors 3712. Fluid flowthrough the device 3700 is described in further detail herein.

FIG. 37J schematically illustrates a side cross-sectional view of anexample of a distal hub 3750 of an expandable structure (e.g., theexpandable structure 3720). The distal hub 3750 may comprise abiocompatible material such as, for example, stainless steel, nitinol,plastic, etc. The distal ends of splines 3722 extend into the distal hub3750. The distal hub 3750 may be generally cylindrical in shape, and mayinclude an atraumatic (e.g., rounded) distal end 3754 and/or a taperedproximal end 3756. The tapered end 3756 may create angled open faces onthe proximal end of the channels 3755 which allow the inserted splines3722 to more easily bend in achieving an expanded configuration. Thedistal hub 3750 may comprise a central lumen 3753 configured to receivean actuator tube 3728. The actuator tube 3728 may be inserted into orthrough the central lumen 3753 and fixably coupled to the distal lumen3753 by any suitable means, such as adhesive (e.g., cyanoacrylate),welding, soldering, combinations thereof, etc. The distal hub 3750comprises a plurality of recesses 3755 configured to receive the distalends of the splines 3722. A recess 3755 may have the same shape as thedistal end of a spline 3722, for example being elongate and cylindrical.The distal hub 3750 may comprise a plurality of recesses 3755 eachconfigured to receive the distal end of one spline 3722. The splines3722 may be rigidly affixed to the distal hub 3750 by welding the distalhub 3750 after the distal ends of the splines 3722 are inserted into therecesses 3755. Welding may comprise applying a heat source around (e.g.,360° around) the outer circumference of the distal hub 3750. Welding maycomprise using a laser and/or another suitable heat source. The splines3722 may be welded to the distal hub 3750. Welding the outercircumference of the distal hub 3750 may, with or without welding thesplines, heat stake the splines 3722 in the recesses 3755 by deformablyreducing the inner diameters of the recesses 3755.

The actuation tube 3728 slidingly extends through the central lumen 3743of the proximal hub 3740, then through a radially inner portion (e.g.,the center) of the expandable structure 3720, then is fixably coupled tothe central lumen 3753 of the distal hub 3750. The distal end of theactuation tube 3728 may be coupled to distal hub 3750 by any suitablemeans, such as adhesive (e.g., cyanoacrylate), welding, soldering,combinations thereof, etc. When the actuation tube 3728 is proximallyretracted, the actuation tube 3728 proximally pulls the distal hub 3750toward the proximal hub 3740, which is held in place by the cathetershaft assembly 3706. As the proximal hub 3740 and distal hub 3750 arebrought closer together, the compressive force on the expandablestructure 3720 forces the splines 3722 to expand radially outwardly,increasing the diameter and/or reducing the length of the expandablestructure 3720. The diameter of the expandable structure may be greaterthan a shape set expanded shape of the expandable structure 3720. Whenthe actuation tube 3728 is distally advanced, the actuation tube 3728distally pushes the distal hub 3750 away from the proximal hub 3740,which is held in place by the catheter shaft assembly 3706. As theproximal hub 3740 and distal hub 3750 are brought further apart, theexpansion force on the expandable structure 3720 forces the splines 3722to retract radially inwardly, decreasing the diameter and/or increasingthe length of the expandable structure 3720.

FIG. 37K shows a side view of an example of a proximal end 3702 of thecatheter system 3700 of FIG. 37A. The proximal end 3702 comprises ahandle 3710 and a portion of a catheter shaft assembly 3706 extendingtherefrom. The handle 3710 is configured to remain outside the body. Thehandle 3710 comprises a proximal part 3761 and a distal part 3762movable relative to the proximal part 3761. The distal part 3762 maycomprise a handle base 3763 and an outer handle 3770. The outer handle3770 may include a grip portion (e.g., comprising a textured surface),which can enhance friction to provide better user grip. The proximalpart 3761 may comprise an actuator 3780 and a hemostasis valve 3784. Theproximal part 3761 and the distal part 3762 may be movably coupled by anactuation tube assembly 3790 and a securing member 3774 comprising alocking member 3776. Electrical conductors 3712 configured to supplysignals to the electrodes 3724 may enter the handle 3710 via connectortubing 3798, which joins the handle 3710 to an electrical socket 3799.The outer handle 3770 may include a projection 3771 with a guide portthrough which the connector tubing 3798 may travel such that theconnector tubing 3798 is secured along the side of the distal part 3762of the handle 3710. The handle 3710 may be asymmetric with respect tothe longitudinal axis of the catheter shaft assembly 3706, which canassist a user in approximating the amount of twisting or rotation in theattached catheter shaft assembly 3706.

FIG. 37L is a side cross-sectional view of the proximal end 3702 of FIG.37K. The outer handle 3770 comprises a recess extending distally fromits distal end that is configured to receive the handle base 3763. Theproximal portion of the handle base 3763 may be partially inserted intothe recess and fixably coupled to the handle base 3763.

The outer handle 3770 comprises a first lumen 3772 configured toslidably receive a portion of the actuation tube assembly 3790. Theouter handle 3770 may include a second lumen 3773 configured to receivea securing member 3774 such as a pin, screw, piston, etc. The securingmember 3774 may comprise, for example, a socket head cap screwcomprising a threaded elongate section and a cap 3775. If the securingmember 3774 is fixably coupled to the actuator 3780, the lumen 3773 maybe devoid of threads so that the securing member 3774 may longitudinallyslide through the lumen 3773. The threaded elongate section may interactwith complementary threads in a lumen of the locking member 3776. If thesecuring member 3774 is rotatably coupled to the actuator 3780, thelumen 3773 may comprise complementary threads, and securing member 3774may longitudinally slide through the lumen 3773 while rotating. Theouter handle 3770 may comprise a shoulder extending into the secondlumen 3773 configured to interact with an enlarged portion of thesecuring member 3774. For example, the shoulder may inhibit or preventproximal retraction of the cap 3775, and thus the securing member 3774,beyond a certain length. Limiting longitudinal translation of thesecuring member 3774, which is fixably coupled to the actuator 3780,which is fixably coupled to the actuation tube 3728, can limit radialexpansion of the expandable member 3720. Limiting radial expansion ofthe expandable member 3720 can enhance safety by reducing the likelihoodof the expandable member 3720 expanding enough to puncture or rupture avessel. The distal end of the lumen 3773 may be occluded, for example toinhibit debris from interfering with movement of the securing member3774. The cap 3775 may comprise a tool interface, for example ahexagonal recess, a protruding nut, etc. The tool interface can be usedduring assembly (e.g., to couple the securing member 3774 to theactuator 3780 and/or during a procedure.

The actuator 3780 may comprise a first lumen 3781 aligned with the firstlumen 3772 of the outer handle 3770. The first lumen 3781 may beconfigured to be coupled to a valve 3784 (e.g., a hemostasis valve 3784(e.g., a luer lock)), for example by comprising complementary threads,being configured to be tapped, being configured to receive a press-fit,etc. The actuator 3780 may comprise a valve in communication with thefirst lumen 3781 that is monolithic with the actuator 3780. A portion ofthe actuation tube assembly 3790 is fixably coupled to at least one ofthe first lumen 3781 and the valve 3784. A lumen of the actuation tubeassembly 3790 may be in fluid communication with a lumen of the valve3784.

The actuator 3780 may comprise a second lumen 3782 configured to fixablycouple the actuator 3780 to the securing member 3774. Depending on theshape and configuration of the securing member 3774, the second lumen3782 may be aligned with the second lumen 3773 of the outer handle 3770.The second lumen 3782 may comprise threads configured to receive andsecure an elongate threaded section of the securing member 3774. Thesecuring member 3774 may be monolithic with and extend from a distalsurface of the actuator 3780.

A locking member 3776 may optionally be positioned along the securingmember 3774 between the actuator 3780 and the outer handle 3770. Thelocking member 3776 may comprise, for example, a locking tuohy (e.g., asillustrated in FIG. 36K), a nut, a wingnut, etc. The locking member 3776comprises a threaded lumen configured to interact with the elongatethreaded section of the securing member 3774. The locking member 3776may comprise a textured outer surface configured to enhance grip of auser. The threads transmit rotational force on the locking member 3776into longitudinal movement along the securing member 3774. When thelocking member 3776 abuts a proximal end of the outer handle 3770, inwhat may be considered a locked position, the locking member 3776inhibits or prevents the actuator 3780 (and thus the actuation tubeassembly 3790 fixably coupled thereto) from moving distally. Locking theactuator 3780 can inhibit or prevent the splines 3722 of the expandablestructure 3720 from radially compressing and losing wall apposition.

The locking member 3776 may comprise any suitable structure forpreventing or inhibiting longitudinal motion of the securing member 3774relative to the outer handle 3770. In some examples, the locking member3776 may be a non-threaded structure. For example, the locking member3776 may comprise a clamp, which is secured to the securing member 3774via pressure and/or friction. The grip of the clamp locking member maybe selectively loosenable and/or tightenable by the user. In someexamples, a clamp locking member 3776 may be biased in a tightenedposition on the securing member 3774 by, for example, a spring. A clamplocking member 3776 may comprise a channel surrounding the circumferenceof the securing member 3774, and the diameter of the channel may beexpanded or reduced by the turning of a screw that joins two ends of aclamp locking member 3776 to close the circumference around the securingmember 3774. A clamp locking member 3776 may comprise a biasedprojection configured to frictionally engage the securing member 3774,and can be temporarily released by the user. A clamp locking member 3776may be slideable or otherwise moveable along the securing member 3774when in a loosened position and not slideable or otherwise moveable whenin a tightened position. In some examples, a clamp locking member 3776may be removable from the securing member 3774 and selectivelyreattached at a desired position along the length of the securing member3774. A clamp locking member 3776 may inhibit or prevent the distaldisplacement of the securing member 3774 relative to the outer handle3770 when a surface of the clamp locking member 3776 abuts the proximalend of the outer handle 3770, placing the handle 3710 in a lockedposition.

FIGS. 37Li-37Liii show an example method of operating a handle 3710 toradially expand an expandable member 3720. FIG. 37Li shows the handle3710 in a compressed state in which the actuator 3780 abuts or is closeto the locking member 3776, which abuts or is close to the outer handle3770. As shown to the left, the expandable member 3720 may be in aself-expanded state. The actuation tube assembly 3790 may proximallyretract upon radially outward self-expansion of the expandable structure3720.

As shown in FIG. 37Lii, as the actuator 3780 is proximally retracted,the securing member 3774, which is fixably coupled to the actuator 3780,slides proximally through the second lumen 3773 of the outer handle3770, the locking member 3776 stays in position on the securing member3774 and thus is proximally retracted, and the actuator tube assembly3790 slides proximally through the catheter shaft assembly 3706, thelumen 3764 of the handle base 3763, and the first lumen 3772 of theouter handle 3770. As the actuator tube assembly 3790 is proximallyretracted, the distal hub 3750 to which the actuator tube 3728 isfixably coupled is proximally retracted, imparting a longitudinallycompressive and radially expansive force on the splines 3722, which isexpanded radially further than the self-expanded state. As the splines3722 appose a vessel wall, the user can typically feel an oppositionforce in the actuator 3780, which is a benefit to a manual proceduresuch as illustrated in FIGS. 37Li-37Liii. Upon feeling the wallapposition, the user may adjust the expansion by further proximallyretracting the actuator 3780 and/or by distally advancing the actuator3780. Once the user is satisfied with the wall apposition provided bythe splines 3722 of the expandable member 3720, the user may engage thelocking member 3776.

As shown in FIG. 37Liii, the user rotates the locking member 3776. Thethreads of the threaded elongate section of the securing member 3774 andthe locking member 3776 translate the rotational force into longitudinalforce, and the locking member 3776 distally advances along the securingmember 3774 until the locking member 3776 abuts a proximal surface ofthe outer handle 3770. If a distal force is applied to the actuator3780, the actuator 3780 generally would not be able to distally movebecause the locking member 3776 is pressing against the proximal surfaceof the outer handle 3770.

FIGS. 37Li and 37Liv show another example method of operating a handle3610 to radially expand an expandable member 3720. Referring again toFIG. 37Li, the handle 3710 is in a compressed state.

As shown in FIG. 37Liv, as the locking member 3776 is rotated, thethreads of the threaded elongate section of the securing member 3774 andthe locking member 3776 translate the rotational force into longitudinalforce. The locking member 3776 bears against the proximal surface of theouter handle 3770, which forces the securing member 3774 to proximallyretract.

As the securing member 3774 is proximally retracted, the securing member3774 slides proximally through the second lumen 3773 of the outer handle3770, the actuator 3780, which is fixably coupled to the securing member3774, proximally retracts, and the actuator tube assembly 3790 slidesproximally through the catheter shaft assembly 3706, the lumen 3764 ofthe handle base 3763, and the first lumen 3772 of the outer handle 3770.As the actuator tube assembly 3790 slides is proximally retracted, thedistal hub 3750 to which the actuator tube 3728 is fixably coupled isproximally retracted, imparting a longitudinally compressive andradially expansive force on the splines 3722, which is expanded radiallyfurther than the self-expanded state. Throughout rotation of the lockingmember 3776, the locking member 3776 bears against the proximal surfaceof the outer handle 3770 such that, if a distal force is applied to theactuator 3780, the actuator 3780 generally would not be able to distallymove because the locking member 3776 is pressing against the proximalsurface of the outer handle 3770.

The force used to rotate the locking member 3776 may provide fine tuningas the locking member 3776 bears against the proximal surface of theouter handle 3770. Depending on the thread pitch, rotation of thelocking member by a certain rotational amount may proximally retract theactuation tube assembly 3790 a certain amount and/or radially expand theexpandable member 3720 a certain amount. For example, a 90° rotation ofthe locking member 3776 may radially expand the expandable member by adiameter of 1 mm in the absence of opposing forces. Finer and coarserpitches are also possible. A finer pitch allows finer tuning. A coarserpitch reduces the amount of rotation used to longitudinally move thecomponents, which can reduce procedure time. The locking member 3776 mayinclude indicia around its circumference to help the user identify theamount of rotation.

Combinations of the methods of FIGS. 37Li-37Liv are also possible. Forexample, the user may first manually retract the actuator 3780, forexample to feel the wall apposition, rotate the locking member 3776 toabut a proximal end of the outer handle 3770, and then fine tune theamount of expansion by rotating the locking member 3776. For example, ifthe user desires to expand the expandable member 3720 by a diameter of 2mm beyond wall apposition (e.g., the diameter of the vessel measure atsystolic maximum), which can provide secure anchoring, the user canrotate the locking member 3776 by 180° after abutting the outer handle3770.

FIG. 37M is a side cross-sectional view of example components of ahandle base 3763. To provide example context, FIG. 37M also includesportions of the actuation shaft assembly 3790, part of the cathetershaft assembly 3706, and connector tubing 3798. The handle base 3763comprises a lumen 3764 configured to receive a sealing element 3766, theactuation tube assembly 3790, and/or the catheter shaft assembly 3706.When the handle base 3763 is inserted into the recess of the outerhandle 3770, the lumen 3764 is aligned with the first lumen 3772 of theouter handle 3770.

The catheter shaft assembly 3706 may be fixably coupled to the handlebase 3763 by inserting the proximal end of the catheter shaft assembly3706 into the lumen 3764 and then securing the catheter shaft assembly3706 to the handle base 3763, for example by adhesive (e.g.,cyanoacrylate), welding, soldering, combinations thereof, etc. Thehandle base 3763 may comprise a shoulder 3768 extending into the lumen3764 configured to interact with the proximal end of the catheter shaftassembly 3706. For example, the shoulder 3768 may provide a stop forinsertion of the catheter shaft assembly 3706 into the lumen 3764, whichcan facilitate manufacturing. The actuation tube assembly 3790 maycomprise a plurality of components, for example including multiple typesof tubing. Fewer components generally may reduce manufacturingcomplexity of the actuation tube assembly 3790. Multiple components canprovide specialization of different portions of the actuation tubeassembly 3790. If coupling components together is easier than modifyingfewer components for particular functions, multiple components canreduce manufacturing complexity of the actuation tube assembly 3790. Theactuation tube assembly 3790 illustrated in FIG. 37M comprises a firsthypotube 3791, a second hypotube 3792, and the actuation tube 3728. Theactuation tube assembly 3790 may comprise an actuation tube assemblylumen 3793 extending from the proximal end of the actuation tubeassembly 3790 to the distal end of the actuation tube assembly 3790. Theactuation tube assembly lumen 3793 may comprise segments in eachcomponent (e.g., the first hypotube 3791, second hypotube 3792, andactuation tube 3728) of the actuation tube assembly 3790, which may bealigned along a longitudinal axis of the actuation tube assembly 3790.The lumens of the components may be joined and/or aligned by, forexample, positioning a component of a smaller outer diameter within thelumen of a component with a larger diameter inner diameter. The innersurfaces of the actuation tube 3728 and/or any of the other componentscomprising the actuation tube assembly lumen 3793 may comprise a lining(e.g., fluoropolymer (e.g., PTFE, PVDF, FEP, Viton, etc.)) to reducefriction with a guidewire inserted through the lumen 3793. The outersurfaces of the actuation tube 3728 and/or any of the other componentscomprising the actuation tube assembly 3790 may comprise a lining (e.g.,fluoropolymer (e.g., PTFE, PVDF, FEP, Viton, etc.)) to reduce frictionbetween the actuation tube assembly 3790 and the catheter shaft assembly3706 or the lumen 3674 of the handle base 3763.

Referring again to FIG. 37L, a proximal end of the actuation tubeassembly 3790, more specifically the proximal end of the first hypotube3791, is fixably coupled to at least one of the actuator 3780 and thevalve 3784. The first hypotube 3791 extends from the actuator 3780 intothe proximal portion of lumen 3764 of the handle base 3763, through thesealing element 3766. The sealing element 3766 provides a fluid-tightseal between the actuation tube assembly 3790 and the handle base 3763.The first hypotube 3791 may be machined to include a first portion 3791Aand a second portion 3791B having a smaller diameter than the firstportion 3791A. The first hypotube 3791 may include one or a plurality ofapertures 3794, which can provide fluid communication between theactuation tube assembly lumen 3793 and the lumen 3764. As described infurther detail herein, fluid (e.g., saline, heparinized saline,contrast, etc.) injected into the lumen 3793 through the valve 3784 canflow through the lumen 3793 until the apertures 3794, and then maycontinue to flow through the lumen 3793 or out of the apertures 3794 andthen through the lumen 3764. In some examples, the first hypotube 3791may be devoid of apertures 3794 and configured such that fluid injectedinto the lumen 3793 flows only through the lumen 3793.

The first portion 3791A of the first hypotube 3791 may have an outerdiameter that is slightly smaller than the inner diameter of the lumen3764. Such a diameter difference can reduce (e.g., minimize) the spacebetween the outer surface of the first portion 3791A and the innersurface of the handle base 3763 to reduce (e.g., minimize) fluid flowingout of the apertures 3794 from flowing proximally and/or can reducefriction between the first portion 3791A and the inner surface of thehandle base 3763. The second portion 3791B of the first hypotube 3791may provide an arcuate or toroidal gap or lumen between an outer surfaceof the second portion 3791B of the first hypotube 3791 and the innersurface of the handle base 3763. Such a diameter difference can promotefluid flowing out of the apertures 3794 to flow distally through thelumen 3764. The first hypotube 3791 may comprise a biocompatiblematerial such as, for example, stainless steel, nitinol, plastic, etc.Although described as a hypotube, the first hypotube 3791 may bemachined from a flat sheet, a solid rod, etc.

A proximal end of the lumen 3764 of the handle base 3763 may include anexpanded diameter portion configured to receive a sealing element 3766(e.g., comprising an o-ring, a shim, a gasket, etc.). The sealingelement 3766 may be positioned between the first hypotube 3791 and thehandle base 3763. The sealing element 3766 can seal a proximal end ofthe lumen 3764 to inhibit or prevent fluid flowing though the apertures3794 from flowing out the handle base 3763.

A second hypotube 3792 may comprise an outer diameter that is slightlysmaller than the inner diameter of the first hypotube 3791 such that aproximal end of the second hypotube may be inserted into a distal end ofthe first hypotube 3791. The second hypotube 3792 may be fixably coupledto the first hypotube 3791, for example by adhesive (e.g.,cyanoacrylate), welding, soldering, combinations thereof, etc. Thesecond hypotube 3792 may extend into a proximal end of the cathetershaft assembly 3706. The outer diameter of the second hypotube 3792 isless than the inner diameter of the lumen 3764, forming an arcuate ortoroidal gap or lumen, which can provide an open segment for fluid toflow and conductors to extend. The second hypotube 3792 may comprise abiocompatible material such as, for example, stainless steel, nitinol,plastic, etc. Although described as a hypotube, the second hypotube 3792may be machined from a flat sheet, a solid rod, etc.

The actuation tube 3728 extends from the proximal portion 3704 of thecatheter system 3700 to the distal portion 3704 of catheter system 3700.The actuation tube 3728 may be fixably coupled to the second hypotube3792, for example by adhesive (e.g., cyanoacrylate), welding, soldering,combinations thereof, etc. The second hypotube 3792 may comprise a lumenhaving an inner diameter that is slightly larger than the outer diameterof the actuation tube 3728 such that a proximal end of the actuationtube 3728 may extend into a distal end of the second hypotube 3792. Thesecond hypotube 3792 may comprise a lumen having an inner diameter thatis slightly larger than the outer diameter of the actuation tube 3728,and a distal end of the second hypotube 3793 may extend into a proximalend of the actuation tube 3728. The actuation tube 3728 may comprise aplurality of layers. For example, the actuation tube 3728 may comprise aflexible polymer (e.g., polyimide, polyamide, PVA, PEEK, Pebax,polyolefin, PET, silicone, etc.), a reinforcing layer (e.g., comprisinga braid, a coil, etc.), and an inner liner (e.g., fluoropolymer (e.g.,PTFE, PVDF, FEP, Viton, etc.)).

The second hypotube 3792 optionally may be omitted, for example byextending the first hypotube 3791 distally and/or extending the flexiblepolymer of the actuation tube 3728 proximally. The second hypotube 3792may comprise a biocompatible material such as, for example, stainlesssteel, nitinol, plastic, etc.

The actuation tube assembly 3790 and the catheter shaft assembly 3706combine to form two concentric lumens between the handle 3710 and theexpandable structure 3720. The actuation tube assembly lumen 3793 of theactuation tube 3728 forms the inner lumen. The inner lumen 3793 may bein fluid communication with the hemostasis valve 3784. The distalterminus of the inner lumen 3793 is the distal end of the actuator tubeassembly 3790, which is coupled to the proximal hub 3740. The hemostasisvalve 3784 may allow insertion of a guidewire, which can extend throughthe actuation tube 3728 and distally beyond the distal hub 3750 of theexpandable structure 3720. The outer lumen 3707 is arcuate or toroidalbetween the outer surface of the actuation tube assembly 3790 and theinner surface of the catheter shaft assembly 3706. The distal terminusof the outer lumen 3707 is the distal end of the catheter shaft assembly3706, which is coupled to the proximal hub 3740.

The hemostasis valve 3784 may be used to inject fluids (e.g., saline,heparinized saline, contrast, etc.). Fluid may be injected into thehemostatsis valve 3784 (e.g., via IV bag, syringe, etc.). The fluid canflow through the first hypotube 3791 until the apertures 3794. The fluidmay continue to flow through the inner lumen 3793 of the actuation tubeassembly 3790 out of the distal hub 3750 and/or may flow through theapertures 3794 and then through the outer lumen 3707 out of the proximalhub 3740. Referring again to FIG. 37G-37I, the proximal hub 3740comprises peripheral lumens 3743. Fluid flows out of the outer lumen3707 through at least one of the peripheral lumens 3743. Fluid flowthrough a peripheral lumen 3743 may be inversely proportional to a levelof occlusion of that peripheral lumen 3743 (e.g., due to occupation byconductors 3712). In some examples, the first hypotube 3791 may notcomprise apertures 3794, and fluid may flow only through the inner lumen3793 of the actuation tube assembly 37990 to the distal hub 3750.

Flushing fluid may provide a slight positive pressure within the lumens,which can inhibit blood from flowing into the catheter system 3700.Flushing fluid may wash the expandable structure 3720 and/or otherportions of the catheter system 3700, which can inhibit thrombusformation during the medical procedure. If the fluid comprises contrast,flushing fluid can direct contrast to aid fluoroscopy and visualizationof the expandable structure 3720 relative to the vessel.

The handle base 3763 may comprise an aperture 3765 extending through asidewall into the lumen 3764, for example in communication with thearcuate or toroidal gap or lumen between the second hypotube 3792 andthe handle base 3763. The conductors 3712 may extend from the electricalconnector 3799, through the connector tubing 3798, through the aperture3765, into the outer lumen 3707, through the proximal hub 3740 (e.g., asshown in FIG. 37I), and to the electrodes 3724.

FIG. 37N is a perspective view of a proximal end of an example of acatheter shaft assembly 3706 and second hypotube 3792. The cathetershaft assembly 3706 surrounds the actuation tube 3728 from the handle3710 to the proximal hub 3740. The actuation tube 3828 may be proximallyretracted and/or distally advanced relative to catheter shaft assembly3706.

The catheter shaft assembly 3706 may comprise a plurality of layers. Forexample, the catheter shaft assembly 3706 may comprise a flexiblepolymer (e.g., polyimide, polyamide, PVA, PEEK, Pebax, polyolefin, PET,silicone, etc.), a reinforcing layer (e.g., comprising a braid, a coil,etc.), and an inner liner (e.g., fluoropolymer (e.g., PTFE, PVDF, FEP,Viton, etc.)). Different layers may be present along differentlongitudinal segments.

The flexible polymer may comprise, for example, polyimide, polyamide,PVA, PEEK, Pebax, polyolefin, PET, silicone, etc.). Differentlongitudinal sections of the tubing may have different durometers alongthe length of the catheter shaft assembly 3706. For example, thecatheter shaft assembly 3706 may transition from a higher durometer,indicating a harder material, to a lower durometer, indicating a softermaterial, from proximal to distal. The lengths and durometers of thevariable durometer sections may be ed to suit the different anatomicalstructures in which those sections will reside during a procedure. Forexample, the catheter shaft assembly 3706 may comprise at least fivedifferent durometer sections: a first section having a durometer ofabout 72 D having a length configured to extend from the handle 3710into the body through a carotid vein proximal to the heart; a secondsection having a durometer of about 63 D and a third section having adurometer of about 55 D together having a length configured to passthrough the right atrium and right ventricle; and a fourth section ofhaving a durometer about 40 D and a fifth section having a durometer ofabout 25 D together having a length configured to extend through thepulmonary valve and into the right pulmonary artery. The flexibility ofthe fourth section and/or the fifth section may allow the catheter shaftassembly 3706 to bend and fixate the catheter shaft assembly, forexample against a left side of the pulmonary trunk, which can aid inproperly positioning the expandable member 3720 in a pulmonary artery.At least one of the fourth section and the fifth section may comprise ahinge 3726, for example as described herein, which can resist kinking ifthe catheter shaft assembly 3706 makes a sharp (e.g.,) 90° turn, forexample from the pulmonary trunk to the right pulmonary artery. Thelengths of the five sections may be, in terms of percentage of the totallength of the catheter shaft assembly 3706, between about 50-90% for thefirst section and between about 1 to 20% for each the remainingsections. For example, the lengths may be about 73%, 7.5%, 5.5%, 5.5%,and 8.5%, respectively. The first section may be longer or shorterdepending on the total length of the catheter shaft assembly 3706, whichmay depend on the pathway to the pulmonary artery, the amount residingoutside the body, etc.

The catheter shaft assembly 3706 may have a length between about 50 and200 cm (e.g., about 50 cm, about 75 cm, about 100 cm, about 125 cm,about 150 cm, about 200 cm, ranges between such values, etc.). Thelength of the catheter shaft assembly 3706 may be suitable to positionthe expandable structure 3720 in a pulmonary artery from a peripheralvein such as a jugular vein, a femoral vein, a radial vein, or othersuitable access location.

The flexibility of the catheter shaft assembly 3706 can be additionallyor alternatively modulated by other means, such as reinforcing andadjusting various sections of the catheter shaft assembly 3706. Forexample, if the catheter shaft assembly 3706 comprises a reinforcingcoil, a pitch of the coil may be varied. For another example, if thecatheter shaft assembly 3706 comprises a reinforcing braid, a parameter(e.g., number, thickness, braid angle, etc.) of the braid wires in maybe varied. For yet another example, the thickness may vary. For stillanother example, the composition may vary (e.g., different sectionscomprising at least one different material). Combinations of two or allvariations is also possible. Rather than being discrete sections, theflexibility may transition from one section to the next section.

FIG. 37N shows the proximal end of catheter shaft assembly 3706comprising a first segment 3708 and a second segment 3709 thicker thanthe first segment 3708. The change in thickness at the proximal end ofthe actuation shaft assembly 3706, for example the first segment 3708,may provide a mechanism of strain relief. The second segment 3709 mayhave an outer diameter configured to fit in the lumen 3764 of the handlebase 3763 to be fixably coupled to the handle base 3763.

FIG. 37O is a side cross-sectional view of an example connection betweena distal end of a catheter shaft assembly 3706 and a proximal hub 3740of an expandable structure 3720. The distal end of the catheter shaftassembly 3706 may comprise a hinge 3726 configured to be fixably coupledto the proximal hub 3740.

The hinge 3726 may comprise, for example, a coil or series ofinterspaced coils that extend slightly beyond the distal end of otherparts of the catheter shaft assembly 3760 such as the PTFE liner, wirebraid, and flexible tubing. The coil hinge 3726 may comprise one or aplurality of wires (e.g., one wire, two wires, three wires, or more)configured in a helical pattern. The wires comprise helically woundcoils having a uniform pitch. Each coil may occupy the space between thehelical revolutions of the other coils. FIG. 37P is a perspective viewof an end of an example of a hinge 3726 comprising three wires. Thehinge 3726 may comprise a hypotube, for example cut to include a coilpattern and/or opposing circumferential slots.

The hinge 3726 may be positioned around the outer surface of theproximal section 3741 of the proximal hub 3740. The hinge 3726 may befixably coupled to the proximal hub 3740 by adhesive (e.g.,cyanoacrylate), welding, soldering, combinations thereof, etc. Thedistal end of the catheter shaft assembly 3706 may comprise layers thatare proximally spaced from the distal end of the hinge 3726 by about0.01 inches to about 0.1 inches (e.g., about 0.01 inches, 0.025 inches,0.05 inches, 0.075 inches, 0.01 inches, ranges between such values,etc.), which can provide sufficient space for the hinge 3726 to beaffixed (e.g., directly affixed) to the proximal hub 3740 withoutinterference from those layers. The distal end of the flexible tubing,wire braid, liner, and/or other layers of the catheter shaft assembly3706 may be longitudinally spaced from the proximal end of the proximalhub 3740, which can reduce transmission of forces on the catheter shaftassembly 3706, for example absorbed by the hinge 3726, from beingtransmitted to the expandable structure 3720.

The hinge 3726 may be covered by a hinge tube 3711, which may compriseurethane or another suitable material, and which extends from the distalend of the hinge 3726 past the proximal end of the hinge 3726, forexample to inhibit pinching of tissue by the hinge 3726. The hinge tube3711 may be heat cured to the hinge 3726 and outer circumference ofother components of the catheter shaft assembly 3706. The hinge tube3711 may be aligned substantially flush with or overlap the distalportion 3742 of the proximal hub 3740. The hinge tube 3711 may form afluid seal with the proximal hub 3742, for example so that fluid flowingin the lumen 3707 exits the peripheral lumens 3744.

FIG. 37Q is a perspective view of an example handle 3701 of a cathetersystem (e.g., the catheter system 3700) in an unlocked configuration.FIG. 37R schematically illustrates a perspective cross-sectional view ofthe handle 3701 of FIG. 37Q along the line 37R. In addition to thehandle 3701, FIGS. 37Q and 37R show a portion of a catheter shaftassembly 3706 extending therefrom. The handle 3701 is configured toremain outside the body. The handle 3701 comprises an outer handle 3713which the user may grasp. The outer handle 3713 comprises a lumen 3714extending from the proximal end of the outer handle 3713 to the distalend of the handle outer 3713. The lumen 3714 may be configured toreceive a tubular base 3715, which may be partially inserted into thelumen 3714 and fixably coupled to the outer handle 3713. The tubularbase 3715 may be generally cylindrical in shape and may comprise atapered distal end. Other geometries (e.g., polygonal) are alsopossible. The tubular base 3715 may extend out of the distal end of thelumen 3714 (as shown in FIGS. 37Q and 37R) or may be entirely receivedwithin the lumen 3714. The tubular base 3715 comprises a channel 3716extending from the proximal end of the tubular base 3715 to the distalend of the tubular base 3715. The tubular base 3715 may comprise ashoulder 3717 extending into the channel 3716 configured to interactwith the proximal end of the catheter shaft assembly 3706. The cathetershaft assembly 3706 may be fixably coupled to the tubular base 3715 byinserting the proximal end of the catheter shaft assembly 3706 into thechannel 3716 and then securing the catheter shaft assembly 3706 to thetubular base 3715, for example by adhesive (e.g., cyanoacrylate),welding, soldering, combinations thereof, etc. The actuation tubeassembly 3790 can be slidably received in the channel 3716 and portionsof the actuation tube assembly 3790 can extend through the cathetershaft assembly 3706, for example as described herein. The tubular base3715 may comprise an annular recess 3718 in the sidewall of the channel3716 positioned near the proximal end of the channel 3716 configured toreceive a sealing element (e.g., comprising an o-ring, a shim, a gasket,etc.) The sealing element may be positioned between the first hypotube3791 and the tubular base 3715, and may inhibit or prevent fluid flowingthrough the apertures 3794 of the first hypotube 3791 from flowing outthe tubular base 3715. In some examples, the annular recess 3718 mayextend to the proximal end of the tubular base 3715.

The proximal end of the actuation shaft assembly 3790 can be coupled toan actuation pin 3730. The actuation pin 3730 comprises an actuationchannel 3731 extending from the proximal end of the actuation pin 3730to the distal end of the actuation pin 3730. The actuation channel 3731is configured to receive the proximal end of the actuation tube assembly3790 (e.g., the first hypotube 3791), which can be partially insertedinto the actuation channel 3731 and fixably coupled to the actuationchannel 3731, for example by adhesive (e.g., cyanoacrylate), welding,soldering, combinations thereof, etc. The actuation pin 3730 maycomprise an expanded diameter grip 3732 for facilitating the grip of theuser. The expanded diameter grip 3732 may comprise a textured surface.The actuation channel 3731 may comprise an expanded diameter portion atits proximal end configured to receive a tubing connector 3797. Thetubing connector 3797 may be Y-shaped, including two intersectingchannels. The channels of the tubing connector 3797 may be used for theinsertion of a guidewire, electrical conductors, and/or the injection offluids into the actuation tube assembly lumen 3793, as describedelsewhere herein. The connector tubing 3797 may comprise a luer fittingincluding a single lumen.

The outer handle 3713 may comprise a void 3719 extending between anupper surface and a lower surface and intersecting the lumen 3714 of theouter handle 3713. In some examples, the void 3719 may extend to a sidesurface of the handle 3713 such that it opens to an upper surface, lowersurface, and side surface of the outer handle 3713. The void 3719 may beconfigured to receive a locking member 3777. FIG. 37S is a perspectiveview of an example of the locking member 3777. The locking member 3777may comprise a generally cylindrical body and a channel 3778 extendingfrom a proximal side of the locking member 3777 to a distal side of thelocking member 3777 through the generally cylindrical body. The lockingmember 3777 may comprise at least one projection 3789 extending radiallyinwardly from the sidewall of the channel 3778. If the locking membercomprises two projections 3789, the two projections 3789 may be onopposite sides of the channel 3778. If the channel 3778 is oblong, theprojection 3778 may be positioned along the longer-dimensioned length ofthe channel 3778 (e.g., at a central position along thelonger-dimensioned length). The locking member 3777 may comprise a tab3779 extending away from the channel 3778, for example in a directionperpendicular to the longitudinal axis of the channel 3778. The tab 3779and generally cylindrical body may form a b-shape, d-shape, p-shape, orq-shape. The actuation pin 3730 may extend through the channel 3778. Thehandle 3701 may comprise a bushing 3796 configured to be received in theproximal end of the outer handle 3713 where the bushing 3796 may beaffixed. The bushing 3796 may comprise a channel through which theactuation pin 3730 extends. The locking member 3777 may be rotatableabout the longitudinal axis of the actuation pin 3730. The lockingmember 3777 can be configured to place the handle 3701 and the actuationtube assembly 3790 in a locked or unlocked configuration. In someexamples, the degree of rotation of the locking member 3777 may belimited. As seen in the example of FIG. 37Q, the tab 3779 may only allowthe locking member 3777 to rotate approximately a quarter-turn beforethe tab 3779 abuts a portion of the outer housing 3713.

FIG. 37T schematically illustrates an expanded perspectivecross-sectional view of the handle 3701 of FIG. 37Q in an unlockedconfiguration in the area of the circle 37T of FIG. 37R. The actuationpin 3730 may comprise a series of ridges 3733 and intervening notchesspaced along its outer circumference. The ridges 3733 may beperpendicular to the longitudinal axis of the actuation pin 3730. Theridges 3733 may extend away from the circumference of the actuation pin3730 along two opposing sides of the actuation pin 3730. For example,the circumference of the actuation pin 3730 may be proportioned intoapproximate quarters, and the ridges 3733 may extend from twonon-adjacent quarters of the circumference. The quarters of thecircumference where the ridges 3733 do not extend may comprise flatsurfaces extending along the length of the actuation pin 3730, as shownin FIG. 37Q (one of the flat surfaces is visible). The projection 3789along the channel 3778 of the locking member 3777 may be configured tobe received in a notch between two of the ridges 3733. The projection3789 may be configured to mate with the outer circumference of theactuation pin 3730 when positioned in a notch. When in an unlockedconfiguration, the rotational orientation of the locking member 3777positions the projection 3789 adjacent to a flattened surface of theactuation pin 3730. As shown in FIG. 37T, the projection 3789 is notpositioned between the ridges 3733 in an unlocked configuration. The tab3779 may be positioned in a first position (e.g., an upward position,extending away from the surface of the outer handle 3713), when in anunlocked configuration. In the unlocked configuration, the actuation pin3730 may be translated in a proximal or distal direction by the user,which causes the translation of the actuation tube assembly 3790, whichis rigidly affixed to the actuation pin 3730. The user may expand theexpandable structure 3720 by pulling the actuation pin 3730 in aproximal direction. The user may compress the expandable structure 3720by pushing the actuation pin 3730 in a distal direction. The expandablestructure 3720 may assume a self-expanded state when in an unlockedconfiguration without a user pushing or pulling on the actuation pin3730. The locking member 3777 may be devoid of a tab 3777, for examplecomprising a textured surface like a thumb wheel.

FIG. 37U is a perspective view of the handle 3701 of FIG. 37Q in alocked configuration. The user may place the handle 3701 in a lockedconfiguration by moving the tab 3779 of the locking member 3777 to asecond position to rotate the locking member 3777 approximately aquarter-turn around the actuation pin 3730. The outer handle 3713 maycomprise a shoulder 3795 (FIG. 37Q) to limit the rotation of the tab3779. In the locked configuration, the tab 3779 may no longer extendaway from the surface of the handle 3701, but may be relatively flushwith the surface of the handle 3701. The different positioning of thetab 3779 in unlocked and locked configurations, as seen in FIGS. 37Q and37U, may provide a visually discernable indicator of the configurationthe handle 3701.

FIG. 37V schematically illustrates a perspective cross-sectional view ofthe handle 3701 of FIG. 37U along the line 37V-37V. When in a lockedconfiguration, the projections 3789 (two projections 3789 in theillustrated example) have been rotated into two of the notches betweenthe ridges 3733 of the actuation pin 3730, inhibiting or preventing theactuation pin 3730 and the actuation tube assembly 3730 coupled theretofrom moving in a proximal direction and from moving in a distaldirection. The locking of the handle 3730 can inhibit or prevent theexpandable structure 3720 from further radially expanding and fromradially compressing. The user may partially turn the tab 3779 at anapproximate desired locking position and may then push or pull on theactuation pin 3779 until the projection 3789 falls into place betweenthe ridges 3733. In some examples, the width of the projections 3789 mayform a tight interference fit with the notches such that a “snap” isfelt when locking or unlocking the locking member 3777. To unlock thelocking member 3777, the user may place the tab 3779 back into anupright position, rotating approximately a quarter-turn in the oppositedirection used to lock the locking member 3777. The locking member 3777may be configured to be turned more or less than a quarter turn toswitch between locked and unlocked configurations.

The handle 3701 can allow the user to quickly and/or easily adjust theexpansion of the expandable structure 3720 by pushing or pulling theactuation pin 3730 a desired amount. The actuation pin 3730 andactuation tube assembly 3790 can be locked in position along thelongitudinal axis according to discrete increments determined by thepitch of the series of ridges 3733 and intervening notches. The pitchand the projection 3789 can be modified to allow either narrower orbroader tuning of the expansion and compression of the expandablestructure 3720 (e.g., the widths can be smaller than shown in FIGS.37Q-37U to provide more locking positions). In some examples, thelocking member 3777 may comprise only one projection 3789 and/or theactuation pin 3730 may comprise only one flattened surface. In someexamples, the actuation pin 3730 may comprise a textured surface (e.g.,comprising grooves, bumps, flanges, etc.) configured to frictionallyengage the locking member 3777. The projection 3789 and notches betweenridges 3733 could be corresponding saw-tooth shapes. In such examples,the locking member 3777 may be configured to allow translation of theactuation pin 3730 (e.g., back to the self-expanded state of theexpandable member 3720 in a failure event) in a locked configuration ifenough force is applied to force the ridges 3733 over the saw toothprojection 3789.

FIG. 38A is a perspective view of an example of a catheter system 3800.The system 3800 may comprise a proximal portion configured to remain outof the body of a subject and a distal portion configured to be insertedinto vasculature of a subject, for example as described with respect tothe catheter system 3800. The system 3800 comprises an expandablestructure 3820. The expandable portion 3820 is coupled to a cathetershaft 3806. In some examples, the system 3800 comprises a strain relief3826 between the catheter shaft 3806 and the expandable structure 3820.The strain relief 3826 may be at least partially in a lumen of thecatheter shaft 3806.

The expandable structure 3820 includes a plurality of splines 3822. Thesplines 3822 comprise a sinusoidal or wave or undulating or zig-sagshape. The sinusoidal shape may provide more flexibility in electrodepositioning. For example, electrodes may be placed at peaks, troughs,and/or rising or falling portions. In some examples, electrodes arepositioned proud of peaks, which can allow the electrodes to make closecontact with vessel walls. The sinusoidal shape may provide better wallapposition, for example creating anchor points at peaks. At least one ofthe splines 3822 comprises an electrode array comprising a plurality ofelectrodes to form an electrode matrix. The number of electrodes in theelectrode matrix, electrode sizing, electrode spacing, etc. may be inaccordance with other systems described herein. In some examples, thesplines 3822 comprise wires having a diameter between about 0.006 inches(approx. 0.15 mm) and about 0.015 inches (approx. 0.38 mm) (e.g., about0.006 inches (approx. 0.15 mm), about 0.008 inches (approx. 0.2 mm),about 0.01 inches (approx. 0.25 mm), about 0.012 inches (approx. 0.3mm), about 0.015 inches (approx. 0.38 mm), ranges between such values,etc.). In some examples, the splines 3822 may be cut from a hypotube andthen shape set into the sinusoidal shape.

FIG. 38B is a perspective view of a portion of the catheter system 3800of FIG. 38A in a collapsed state. The illustrated portion includes partof the catheter shaft 3806, the strain relief 3826, and the expandablestructure 3820. The illustrated portion also includes an actuationmember 3828, which can be coupled to an actuator mechanism to causeexpansion or retraction of the expandable structure 3820. The actuationmember 3828 may be in a lumen of the catheter shaft 3806. A guidewire3815 is also shown in the lumen of the actuation member 3828. In someexamples, the actuation member 3828 comprises a lumen capable ofreceiving a 0.018 inch guidewire 3815. The actuation member 3828 maycomprise a tubular structure, for example as described with respect tothe actuation tube assembly 3790. The actuation member 3828 may comprisea wire with or without a lumen.

FIG. 38C is a side view of a portion of the catheter system 3800 of FIG.38A in an expanded state. Operation of the actuation mechanism 3612 cancause the expandable structure 3620 to expand and contract. For example,rotation and/or longitudinal movement of the actuation mechanism 3612can cause the actuator wire 3628 to proximally retract, the cathetershaft 3606 to distally advance, or a combination thereof, each of whichcan push the splines 3622 radially outward. In some examples, the distalends of the splines 3622 are coupled to a distal hub that is coupled tothe actuator wire 3628, and the proximal ends of the splines 3622 arecoupled to a proximal hub that is coupled to the catheter shaft 3606. Inthe expanded state, the expandable structure 3620 comprises splines 3622that are spaced from each other generally parallel to a longitudinalaxis at a radially outward position of the splines 3622. The parallelorientation of the splines 3622 can provide circumferential spacing ofthe splines 3622, for example in contrast to singular splines or wiresthat may circumferentially bunch. In some examples, the splines 3622comprise wires having a diameter between about 0.006 inches (approx.0.15 mm) and about 0.015 inches (approx. 0.38 mm) (e.g., about 0.006inches (approx. 0.15 mm), about 0.008 inches (approx. 0.2 mm), about0.01 inches (approx. 0.25 mm), about 0.012 inches (approx. 0.3 mm),about 0.015 inches (approx. 0.38 mm), ranges between such values, etc.).

In some examples, the diameter of the expandable structure 3820 in theexpanded state is between about 15 mm and about 30 mm (e.g., about 15mm, about 20 mm, about 22 mm, about 24 mm, about 26 mm, about 28 mm,about 30 mm, ranges between such values, etc.). In some examples, thesplines 3822 may be self-expanding such that an actuation mechanismallows the splines to self-expand from a compressed state for navigationto a target site to an expanded state for treatment at the target site.In certain such examples, the diameter of the expandable structure 3820in the expanded state may be oversized to most the intended vasculatureof most subjects to ensure vessel wall apposition. In some examples, thesplines 3822 may be non-self-expanding such that the splines only expandupon operation of an actuation mechanism. In some examples, the splines3822 may be self-expanding, and an actuation mechanism may furtherexpand the splines 3822, which may provide an adjustable expandablestructure 3820 diameter usable for a range of vessel sizes, wallapposition forces, etc. Examples in which the expandable structure 3820does not appose the wall in the event of an error could be advantageousfor safety, for example as described with respect to the system 2200.

FIG. 38D is a partial side cross-sectional view of the expandablestructure 3820. The expandable structure comprises a distal hub 3830comprising a plurality of channels 3832 in which the distal segments ofthe splines 3822 are positioned. In some examples, the distal segmentsof the splines 3822 are not fixed such that they can slide in thechannels 3832, which can allow each spline 3822 to move independently,which may accommodate curvature at a deployment site. In certain suchexamples, the distal ends of the splines 3822 comprise a stop member(e.g., an expanded diameter ball weld) that inhibits or prevents thedistal segments from exiting the channels 3832 and the distal hub 3830.Such a system may also be used with other catheter systems andexpandable structures described herein (e.g., the expandable structures3620, 3630, 3640, 3650).

FIG. 38E is a partial side cross-sectional view of an expandablestructure 3840. The expandable structure 3840 comprises a plurality ofsplines 3842 having a sinusoidal shape. The expandable structure 3840comprises a plurality of electrodes 3844 at peaks of a plurality ofthree of the splines 3842 to form a 3 x 4 electrode matrix. In someexamples in which three splines comprise electrodes, a middle or centralspline may be different than the circumferentially adjacent splines. Forexample, the middle spline may comprise more or fewer peaks, peaks thatare longitudinally offset, etc. Upon expansion of the expandablestructure 3820, the electrodes of the electrode matrix may beselectively activated for testing nerve capture, calibration, and/ortherapy, for example as described herein.

FIG. 39A is a side view of an example of an expandable structure 3900.The expandable structure 3900 may be incorporated into a catheter systemsuch as the catheter systems described herein. The expandable structure3900 comprises a plurality of splines 3902. The splines 3902 are bent toform parallel portions 3904 that are radially offset. The parallelportions 3904 may comprise electrodes, electrode structures, etc. Insome examples, bent portions of the splines act as hinges to urge theoffset parallel portions 3904 against vessel walls. The expandablestructure 3900 may be self-expanding, expandable using an actuationmechanism, and combinations thereof, for example as described herein.FIG. 39A illustrates four splines 3902 that are circumferentially offsetby about 90 °, but other numbers of splines and offset are alsopossible.

FIG. 39B is an end view of an example of another expandable structure3910. The expandable structure 3910 comprises six splines 3912, three ofwhich are grouped on one side of a plane 3914 and three of which aregrouped on the other side of the plane 3914. In some examples, one groupof splines 3912 may comprise electrodes and the other group of splines3912 may be free of electrodes and used for wall apposition, anchoring,etc. In some examples, FIG. 39B is representative of a portion of FIG.36H. For example, the expandable structures 3900, 3910 may comprise aportion (e.g., half) of the splines described with respect to FIGS.36A-36O.

FIG. 39C is an end view of an example of yet another expandablestructure 3920. The expandable structure 3920 comprises six splines 3922and six splines 3924. Like the splines 3902, the splines 3922 compriseradially offset parallel portions. The splines 3924 are each generallyparallel to an adjacent spline up to the bend, and continue to extendradially outward.

FIG. 39D is an end view of an example of still another expandablestructure 3930. The expandable structure 3930 comprises a first spline3932, a second spline 3934, and six splines 3936 Like the splines 3902,the spline 3922 comprises a radially offset parallel portion. Like thesplines 3902, the spline 3924 also comprises a radially offset parallelportion that is radially offset in a different direction than the spline3922. The splines 3936 are extend radially outward, with one spline 3936circumferentially between the splines 3932, 3934. The splines 3932,3934, and the spline 3936 circumferentially between the splines 3932,3934 may comprise electrodes forming an electrode matrix. In someexamples, FIG. 39D is representative of a portion of FIG. 36L. Forexample, the expandable structures 3900, 3910, 3920, 3930 may comprise aportion (e.g., half) of the splines described with respect to FIGS.36A-36O.

The parallel portions of the expandable structures 3900, 3910, 3920,3930 may be straight, recessed, crowned, sinusoidal, longitudinallyoffset, carrying a mesh, etc., for example as described herein.

FIG. 40A is a perspective view of an example of a strain relief 4026 fora catheter system. The strain relief 4026 can act like a flexible hingeto decouple catheter forces from an expandable structure, for example inthe catheter systems described herein. The strain relief 4026 comprisesa spring. The spring may comprise a variable helix, which can varyflexibility longitudinally. In some examples, the spring may be embeddedin a polymer. In some examples, the polymer may have a durometer thatvaries longitudinally in longitudinal alignment with and/orlongitudinally offset from helix variability. In some examples, a strainrelief does not comprise a spring, but comprises a polymer havinglongitudinally varying durometer. In some examples, a plurality ofhelices of opposite sense may be braided to form a strain relief.

FIG. 40B is a perspective view of another example of a strain relief4027 for a catheter system. The strain relief 4027 can act like aflexible hinge to decouple catheter forces from an expandable structure,for example in the catheter systems described herein. The strain relief4027 comprises a cut hypotube. In the example illustrated in FIG. 40B,the cut comprises a first helix 4002 having a first sense (e.g., windingclockwise) and a second helix 4004 having the same first sense. Thefirst helix 4002 is longitudinally offset from the second helix 4004. Insome examples, the cut pattern may comprise a variable helix, which canvary flexibility longitudinally. In some examples, the hypotube may beembedded in a polymer. In some examples, the polymer may have adurometer that varies longitudinally in longitudinal alignment withand/or longitudinally offset from helix variability. Other cut patternsare also possible. For example, the cut pattern may comprise a singlehelix. For another example, the cut pattern may comprise a plurality oftransverse slots or kerfs connected by one or more struts. In sineexamples, a cut hypotube may provide tensile strength.

FIG. 41A is a perspective view of an example of a catheter system 4100.The system 4100 comprises a proximal portion 4102 configured to remainout of the body of a subject and a distal portion 4104 configured to beinserted into vasculature of a subject. The distal portion 4104comprises a first expandable structure 4120 and a second expandablestructure 4122. The proximal portion comprises an actuation mechanism4112. The proximal portion 4102 is coupled to the distal portion 4104 bya catheter shaft 4106. In some examples, the catheter shaft is slightlyrigid such that the catheter shaft 4106 can appose a sidewall and helpto anchor the system 4100 at a target position. The proximal portion4102 may comprise an adapter comprising a plurality of ports, forexample the Y-adapter comprising a first Y-adapter port 4116 and asecond Y-adapter port 4118. The first Y-adapter port 4116 may be incommunication with a lumen in fluid communication with the secondexpandable member. The second Y-adapter port 4118 may be used to couplean electrode matrix of the system 4100 to a stimulator system 4119. Insome examples, the proximal portion 4102 comprises a stimulator system4119. For example, the proximal portion 4102 may comprise electronicsconfigured to provide stimulation to an electrode matrix, sensors (e.g.,in communication with a fluid filled lumen of the catheter shaft 4106),electronics to receive data from sensors, electronics for closed loopcontrol, electronics to provide feedback to a user (e.g., physician,nurse, subject), input mechanisms for a user (e.g., physician, nurse,subject), etc.

FIG. 41B is a perspective view of a portion 4104 of the catheter system4100 of FIG. 41A in a collapsed and deflated state. FIG. 41C is atransverse cross-sectional side view of the portion 4104 of FIG. 41B.The illustrated distal portion 4104 includes part of the catheter shaft4106, the first expandable structure 4120, the second expandablestructure 4122, and a tubular member 4128. The first expandablestructure 4120 includes a plurality of splines coupled to the cathetershaft 4106. The tubular member 4128 may be in a lumen of the cathetershaft 4106. In some examples, the distal ends of the splines are coupledto a distal hub that is coupled to the tubular member 4128, and theproximal ends of the splines are coupled to the catheter shaft 4106.Distal segments of the splines may be slidable in a distal hub, forexample as described herein. The tubular member 4128 comprises a lumen4129. The lumen 4129 is in fluid communication with the secondexpandable member 4122.

The second expandable member 4122 may be adjacent to the firstexpandable member 4120 (e.g., distance of 0 cm) or longitudinally(proximally or distally) spaced from the first expandable member 4120 byup to about 5 cm (e.g., about 0.25 cm, about 0.5 cm, about 1 cm, about1.5 cm, about 2 cm, about 2.5 cm, about 3 cm, about 4 cm, about 5 cm,ranges between such values, etc.). The amount of spacing, if any, may atleast partially depend on the location of a target site, the stiffnessof the catheter shaft 4106, the number of splines of the firstexpandable member 4120, the expanded diameter of the first expandablemember 4120, etc.

FIG. 41D is a side view of the portion of 4104 of FIG. 41B in aninflated state. Specifically, the second expandable member 4122 isinflated. In some examples, fluid (e.g., saline, contrast, etc.) may beinjected into the lumen 4129 until the second expandable member 4122radially expands. In some examples, the second expandable member 4122may longitudinally expand. The inflated second expandable member 4122may be a Swan-Ganz balloon, which can be used to float the distalportion 4104 to a target site such as a pulmonary artery. Rather thantracking a guidewire through the catheter system 4100, the cathetersystem 4100 may comprise an all-in-one system in which the secondexpandable member comprises an electrode matrix. In some examples, thecatheter system 4100 may be devoid of a second expandable member 4122and/or may be configured to track over a guidewire, which may bepositioned in vasculature (e.g., in the right pulmonary artery 4143)prior to introduction of the catheter system 4100, for example asdescribed herein using a Swan-Ganz technique, fluoroscopy-guidedsteering, etc.

FIG. 41E is a perspective view of the portion of 4104 of FIG. 41B in anexpanded state. Specifically, the first expandable member 4120 isexpanded. In some examples, operation of the actuation mechanism 4112can cause the first expandable structure 4120 to expand and contract.For example, rotation and/or longitudinal movement of the actuationmechanism 4112 can cause the tubular member 4128 to proximally retract,the catheter shaft 4106 to distally advance, or a combination thereof,each of which can push the first expandable member 4120 radiallyoutward. In certain such examples, the tubular member 4128 can inflatethe second expandable member by flowing fluid through the lumen 4129 andcan expand the first expandable member 4120 by proximally retracting. Adual function tubular member 4128 may reduce mass and/or complexity ofthe catheter system 4100. In some examples, different structures can beused to accomplish one or more of these functions. For example, in someexamples, the splines may be self-expanding such that the actuationmechanism 4112 or another mechanism (e.g., retraction of a sheath overthe splines) allows the splines to self-expand from a compressed statefor navigation to a target site to an expanded state for treatment atthe target site. In certain such examples, the diameter of the firstexpandable structure 4120 in the expanded state may be oversized to mostthe intended vasculature of most subjects to ensure vessel wallapposition. In some examples, the splines may be non-self-expanding suchthat the splines only expand upon operation of the actuation mechanism4112. In some examples, the splines may be self-expanding, and theactuation mechanism 4112 may further expand the splines, which mayprovide an adjustable first expandable structure 4120 diameter usablefor a range of vessel sizes, wall apposition forces, etc. Examples inwhich the first expandable structure 4120 does not appose the wall inthe event of an error could be advantageous for safety, for example asdescribed with respect to the system 2200. In some examples, the wiresare not fixed distally (e.g., to a distal hub), which can allow eachwire to move independently, which may accommodate curvature at adeployment site.

In the expanded state, the first expandable structure 4120 comprisessplines that are circumferentially spaced from each other on one side ofa plane that includes a longitudinal axis of the distal portion 4104. Insome examples, the splines comprise wires having a diameter betweenabout 0.006 inches (approx. 0.15 mm) and about 0.015 inches (approx.0.38 mm) (e.g., about 0.006 inches (approx. 0.15 mm), about 0.008 inches(approx. 0.2 mm), about 0.01 inches (approx. 0.25 mm), about 0.012inches (approx. 0.3 mm), about 0.015 inches (approx. 0.38 mm), rangesbetween such values, etc.). In some examples, the diameter of theexpandable structure 4120 in the expanded state is between about 15 mmand about 30 mm (e.g., about 15 mm, about 20 mm, about 22 mm, about 24mm, about 26 mm, about 28 mm, about 30 mm, ranges between such values,etc.).

The splines of the first expandable member 4120 may comprise anelectrode array comprising a plurality of electrodes to form anelectrode matrix. The number of electrodes in the electrode matrix,electrode sizing, electrode spacing, etc. may be in accordance withother systems described herein. For example, in some examples, theexpandable structure 4120 comprises a mesh or membrane comprisingelectrodes that is stretched across two or more of the splines. Uponexpansion of the first expandable structure 4120, the electrodes of theelectrode matrix may be selectively activated for testing nerve capture,calibration, and/or therapy, for example as described herein.

FIG. 41F schematically illustrates the first expandable structure 4120expanded in vasculature. The vasculature may include, for example, apulmonary trunk 4132, a right pulmonary artery 4134, and a leftpulmonary artery 4136. In some examples, the catheter 4106 is asymmetricsuch that the catheter shaft 4106 can bend during floating to naturallyalign the first expandable structure 4120 with the right pulmonaryartery 4134. After expansion of the first expandable structure 4120, thecatheter system 4100 may be proximally retracted until the firstexpandable structure 4120 snaps into place. Upon positioning of thefirst expandable member 4120, electrodes on splines of the firstexpandable structure 4120 may be used to stimulate a target nerve 4138.

FIG. 41G schematically illustrates another example of the firstexpandable structure 4120 expanded in vasculature. The vasculature mayinclude, for example, a pulmonary trunk 4132, a right pulmonary artery4134, and a left pulmonary artery 4136. The bending and positioning ofthe tubular member 4128 against the left side of the pulmonary trunk4132 may position and anchor the first expandable structure 4120 in theright pulmonary artery 4134 in a position for stimulating a target nerve4138.

In some examples, expansion of the first expandable structure 4120 bendsthe distal portion 4104 relative to the catheter shaft 4106. Thisbending may advantageously help to anchor the distal portion 4104 at atarget site. For example, the tubular member 4128 can appose a firstside of a vessel and the catheter shaft 4106 can appose an opposite sideof the vessel.

FIG. 42A is a side view of an example of an electrode structure 4224.The electrode structure 4224 may be used with expandable structures asdescribed herein. In FIG. 42A, the electrode structure 4224 is shown ona spline 4222 of an expandable structure. The electrode structure 4224comprises a plurality of electrodes 4202 and insulation 4204 around theelectrodes 4202. The electrodes 4202 extend around the circumference ofthe electrode structure 4224. The electrode structure 4224 may be formedseparately and then slid over the spline 4222.

FIG. 42B is a side view of another example of an electrode structure4225. The electrode structure 4225 may be used with expandablestructures as described herein. In FIG. 42B, the electrode structure4225 is shown on a spline 4222 of an expandable structure. The electrodestructure 4225 comprises a plurality of electrodes 4203 and insulation4204 around the electrodes 4203. The electrodes 4203 extend partiallyaround the circumference of the electrode structure 4225. The electrodestructure 4225 further comprises insulation 4205 on an inner side, whichcan insulate the electrodes 4203 and direct energy radially outward. Theelectrode structure 4225 may be formed separately and then slid over thespline 4222.

FIG. 43A is a side view of an example of an electrode 4302. Theelectrode 4302 is a button electrode that may be coupled to a spline ora mesh. The electrode 4302 does not comprise insulation such that energymay be emitted in all directions.

FIG. 43B is a side view of another example of an electrode 4303. Theelectrode 4303 is a button electrode that may be coupled to a spline ora mesh. The electrode 4303 comprises insulation 4305 such that energy isemitted from uninsulated areas, which can provide directional control.

FIG. 44A is a side view of an example of an electrode 4402. Theelectrode 4402 is a barrel electrode that may be coupled to a spline ora mesh. The electrode 4303 does not comprise insulation such that energymay be emitted in all directions.

FIG. 44B is a side view of another example of an electrode 4403. Theelectrode 4403 is a barrel electrode that may be coupled to a spline ora mesh. The electrode 4403 comprises insulation 4405 such that energy isemitted from uninsulated areas, which can provide directional control.In some examples, the rotational position of the electrode 4403 around aspline is fixed, for example to direct energy radially outward.

FIG. 45 is a schematic diagram of neurostimulation of a nerve proximateto a vessel wall. An electrode 4508 is positioned in a vessel cavity4506, and the vessel wall 4504 is proximate to or adjacent to a nerve4502. The electrode 4508 is partially insulated (e.g., as in theelectrode 4303) such that energy primarily radiates from one side. Theelectrode 4508 may have an area between about 1 mm² and about 3 mm². Insome examples, the electrode 4508 comprises platinum iridium. In someexamples, the uninsulated surface of the electrode 4508 is treated, forexample to increase surface area. The energy radiates from the surfaceof the electrode 4508 and dissipates in the vessel wall 4504. A portionof the energy radiates out of the vessel wall 4504 and captures part ofthe nerve 4502. The nerve 4502 also dissipates the energy, which doesnot extend far beyond the nerve 4502, which could reduce the chances ofcapturing other undesired or unintended nerves, which could reduce sideeffects such as pain, cough, etc. The nerve may have a diameter 4503between about 1 mm and about 2 mm. Even with insulation, some energy maybe emitted from the opposite surface into the vessel cavity 4506, whereblood or other materials may dissipate the energy.

Table 1 shows the correlation between changes in right ventriclecontractility and left ventricle contractility after three differentchanges. The correlation was a heartbeat-by-heartbeat analysis. Pressuremeasurements, taken by a Millar catheter comprising a MEMS pressuresensor, in units of max (dP/dt) was used as a surrogate forcontractility.

The first change, a dobutamine injection, provided a very highcontractility increase greater than 500%. The average correlationbetween right ventricle contractility and left ventricle contractilitywas very good at 0.91, where 1.00 is a perfect correlation. Accordingly,if a subject is given a dobutamine injection, measuring changes to rightventricle contractility can provide accurate information about changesto left ventricle contractility. The first change was repeated threetimes.

The second change, calcium injection at 5 mL, provided a contractilityincrease of about 20%. FIG. 46A shows the left ventricle pressure inblue as measured by a Millar Mikro-Cath (MEMS) pressure sensor catheter,right ventricle pressure as measured by a pressure sensor incommunication with a fluid filled lumen in yellow, and right ventriclepressure in purple as measured by a Millar Mikro-Cath (MEMS) pressuresensor catheter, as well as arterial pressure in green as measured inthe aorta by a Millar Mikro-Cath (MEMS) pressure sensor catheter. Theaverage correlation between right ventricle contractility and leftventricle contractility using a Millar (MEMS) sensor on a catheter wasvery good at 0.91. The average correlation between right ventriclecontractility and left ventricle contractility using a fluid-filledlumen of a Swan-Ganz catheter in communication with an external pressuresensor was also very good at 0.87. Accordingly, under certaincircumstances such as measurement of an animal (normal, non-HF ovinemodel) model, if a subject is given a calcium injection, measuringchanges to right ventricle contractility with a MEMS sensor or a fluidfilled lumen can provide accurate information about changes to leftventricle contractility.

The fourth change, neurostimulation as described herein, provided acontractility increase of about 28%. The correlation between rightventricle contractility and left ventricle contractility was very goodat 0.90. Accordingly, if a subject is given neurostimulation, measuringchanges to right ventricle contractility can provide accurateinformation about changes to left ventricle contractility. FIG. 46Bshows the left ventricle contractility in teal and the right ventriclecontractility in gold for the neurostimulation change in which theneurostimulation was applied after about 35 seconds and then cut offafter being applied for about 2 minutes. In the first several beatsafter the calcium injection, the left ventricle contractility increaseddramatically, but the right ventricle contractility only slightlyincreased. Thereafter, the left ventricle contractility tapered offlogarithmically or exponentially, but the right ventricle contractilitydecreased very slowly. These differences help to show why thecorrelation between left ventricle contractility and right ventriclecontractility are poorly correlated for calcium injections. The fourthchange was not repeated.

TABLE 1 Change Average R-Value Contractility % Increase DobutamineInjection 0.91 >500 Calcium Injection (5 mL) 0.91 (Millar) ~20 0.87(Fluid Filled) Neurostimulation 0.90 ~28

In some examples, a MEMS pressure sensor can be integrated into thecatheter systems described herein, for example configured to reside inthe right ventricle to measure right ventricle contractility, which canbe accurately correlated to left ventricle contractility forneurostimulation. In some examples, an alternative pressure measurementsystem, for example a fluid-filled (e.g., saline-filled) lumen having afirst end in communication with an external pressure sensor (e.g.,connected via a luer fitting) and a second end in communication with anaperture configured to reside in the right ventricle to measure rightventricle contractility, which can be accurately correlated to leftventricle contractility for neurostimulation. MEMS pressure sensors mayprovide higher fidelity (more immediate feedback) than pressure sensinglumens. MEMS pressure sensors may occupy less catheter volume becausethey do not include a lumen, which can reduce the size of the catheterand/or provide additional space for other devices. MEMS pressure sensorsmay be easier to set up, for example compared to filling a lumen withfluid and correctly coupling the fluid filled lumen to a sensor. MEMSpressure sensors may be easier to place anatomically. Easier set upand/or placement may lead to more accurate results. MEMS pressuresensors may reduce or eliminate a whip effect in which curvature of afluid filled lumen may kink when bending around a curve, which canprovide inaccurate readings. Pressure sensing lumens may advantageouslybe well suited for long dwell times, as they are less likely to beaffected by blood than MEMS sensors. In some examples, multiple pressuresensors, of the same type or different types, may be used, for exampleto provide a more accurate measurement (e.g., by taking an average or aweighted average of the measurements).

The accuracy of measurement of left ventricle contractility by measuringright ventricle contractility during neurostimulation can be used tomonitor therapy efficacy. The accuracy of measurement of left ventriclecontractility by measuring right ventricle contractility duringneurostimulation can be used to monitor therapy efficacy. In someexamples, left ventricle contractility, after correlation from ameasurement of right ventricle contractility, can be used for closedloop control (e.g., neurostimulation parameter adjustments, turningneurostimulation on and/or off, etc.).

In some examples, pressure such as right ventricle pressure can bemonitored for safety purposes. For example, right ventricle pressure,correlated left ventricle pressure, and optionally other measurementssuch as right atrium pressure can be used as a surrogate ECG signal fordetermining heart rate and/or arrhythmias. As described below, suchvariables may not be normally measurable during stimulation.

For another example, pressure can be used to determine if a catheter hasmoved, for example from the right ventricle into the right atrium or thesuperior vena cava, or from the pulmonary artery into the rightventricle. The system may be configured to trigger (e.g., automatically)certain events upon determination of movement, such as stoppingstimulation, collapsing an electrode basket, releasing an anchor, etc.

FIG. 47A schematically illustrates an example electrocardiograph (ECG orEKG). The ECG includes a P wave, a Q wave, a R wave, a S wave, and a Twave, which are indicative of different events during a single heartbeatof a healthy patient. The P wave represent atrial depolarization, whichcauses the left atrium and the right atrium to push blood into the leftventricle and right ventricle, respectively. The flat period until the Qwave, the “PR Segment,” and the start of the P wave to the start of theQ wave is the “PR Interval.” The Q wave, the R wave, and the S wave,together the “QRS Complex,” represent ventricular depolarization, whichcauses the right ventricle to push blood into the pulmonary artery andtowards the lungs and which causes the left ventricle to push blood intothe atrium for distribution to the body. The T wave representsrepolarization of the left and right ventricles. The flat period untilthe T wave is the “ST Segment” during which the ventricles aredepolarized, and collectively the QRS Complex, the ST Segment, and the Twave are the “QT Interval.” Some ECGs also have a U wave after the Twave. The timing, amplitude, relative amplitude, etc. of the variouswaves, segments, intervals, and complexes can be used to diagnosevarious conditions of the heart. Electrical stimulation from the systemsdescribed herein may interfere with a normal ECG. In some examples, theECG signal may be modified to account for such interference.

In some examples, the ECG may be monitored by the system so thatstimulation is only applied during, for example, the period between theT wave and the P wave, the period between the S wave and the P wave, theperiod between the S wave and the Q wave, etc. The ECG may beartificially flatlined during periods of stimulation but unaffectedduring periods of non-stimulation. Some users may prefer to see aflatline or “blank” period rather than noise, an artificial signal, etc.In some examples, the ECG may be flatlined artificially high or low orshow an irregular pattern during periods of stimulation so that a userof the ECG recognizes that the signal during such periods is notaccurate. FIG. 47B is an example of a modified electrocardiograph.During stimulation, which occurs in the period between the S wave andthe T wave, the ECG is artificially low.

FIG. 47C is an example of a monitored electrocardiograph. As discussedabove, the stimulation is timed to heartbeats. Rather than relying onthe heartbeat, including intrabeat duration, remaining regular,stimulation is applied for a portion of the time between heartbeats,after which the ECG is monitored for the next beat. For example,stimulation is applied for a short period after S wave (represented by“S” in FIG. 47C), followed by a monitoring period where the P waveshould begin or be completed (represented by “M” in FIG. 47C). If the Pwave is detected, then stimulation and monitoring are repeated. If the Pwave is not detected in the monitoring period, which may be indicativethat something is wrong, stimulation can be stopped. Stimulation may berestarted by a user after determining that conditions are appropriatefor stimulation. Stimulation may be restarted automatically by thesystem after a certain number of normal heartbeats following theaberration.

In some examples, for example in which the stimulation system has a lowduty cycle such as 1 second ON and 5 seconds OFF, 5 seconds ON and 10seconds OFF, etc., the ECG may be halted during the period ofstimulation and replaced with an alternative reading.

FIG. 47D is an example of a modified electrocardiograph. Duringstimulation, the entire electrocardiograph is flatlined. In someexamples, the ECG may be flatlined artificially high or low so that auser of the ECG recognizes that the signal during such periods is notaccurate.

FIG. 47E is another example of a modified electrocardiograph. Duringstimulation, the duration of which is known in advance, theelectrocardiograph from the period preceding the stimulation is copiedand presented again as the ECG during stimulation. FIG. 47F is stillanother example of a modified electrocardiograph. During stimulation, anartificial ECG, for example based on other patient data such aspressure, a perfect ECG, etc., is presented as the ECG duringstimulation. In some examples based on pressure data, the artificialportion of the ECG may comprise or alternatively consist essentially ofa R wave indicative of left ventricle contraction. The modified ECG ofFIGS. 47E and 47F may allow integration with other machinery, forexample which might alarm or function improperly if an ECG varied from anormal ECG.

FIG. 47G is yet another example of a modified electrocardiograph. Duringstimulation, an artificial ECG that is known to be artificial byvisualization. For example, rather than waves with peaks, the waves maybe represented as square waves. The modified ECG of FIG. 47G may allowintegration with other machinery, for example which might alarm orfunction improperly if an ECG varied from a normal ECG, and/or can bevisualized and clearly known to not be representative of actual ECGdata.

In some examples, the effect of the stimulation on the ECG can befiltered out to present a true ECG during periods of stimulation.

Certain safety systems for the catheter systems are described herein,for example collapsing to a retracted state. In some examples, aparameter may be monitored, and certain events can be effected inresponse to a monitored parameter exceeding a threshold.

In some examples, the monitored parameter comprises pressure from apressure sensor configured to be in the pulmonary artery. A pressuredeviating from pulmonary artery pressure may indicate that the catheterhas slid back such that electrodes may be in the right ventricle. Eventsthat may be effected include stopping stimulation, collapsing anexpandable member, and/or sounding an alarm (e.g., sending a wirelessmessage). In some examples, right ventricle pressure may be monitored toconfirm that the deviating pressure shows right ventricle pressure.Other combinations of sensor positions and vascular pressures, forexample between a downstream cavity and an upstream cavity, are alsopossible. For example, right pulmonary artery to pulmonary artery, leftpulmonary artery to pulmonary artery, pulmonary artery to rightventricle, right ventricle to right atrium, right atrium to superiorvena cava, right atrium to inferior vena cava, superior vena cava toleft brachiocephalic vein, superior vena cava to right brachiocephalicvein, left brachiocephalic vein to left internal jugular vein, rightbrachiocephalic vein to right internal jugular vein, combinationsthereof, and the like.

In some examples, the monitored parameter comprises movement from amovement sensor. The pressure sensor may comprise, for example, acapacitive sensor, a magnetic sensor, a contact switch, combinationsthereof, and the like. In some examples, the movement sensor ispositioned at the access point (e.g., a left internal jugular vein).Movement greater than a certain distance (e.g., greater than about 0.5cm, greater than about 1 cm, or greater than about 2 cm) may triggereffect events including stopping stimulation, collapsing an expandablemember, and/or sounding an alarm (e.g., sending a wireless message). Insome examples, a plurality of movement sensors spaced longitudinallyalong the system may be used to verify the detected movement.

In some examples, the monitored parameter comprises heart rate. Asdescribed herein, a pressure waveform may be used to monitor heart rateduring stimulation. Other methods of monitoring heart rate duringstimulation are also possible. If the heart rate changes by a certainamount or percentage, events that may be effected include stoppingstimulation, collapsing an expandable member, and/or sounding an alarm(e.g., sending a wireless message).

In some examples, the monitored parameter comprises electrode impedance.If an electrode is configured to be pressed against a vessel wall, orspaced from the vessel wall by a distance, that configuration results inan impedance. If the impedance changes by a certain amount orpercentage, events that may be effected include stopping stimulation,collapsing an expandable member, using an unused electrode, and/orsounding an alarm (e.g., sending a wireless message).

FIG. 47Hi schematically illustrates an example system for blankingneurostimulation from an ECG. As discussed herein, application ofneurostimulation to a subject 4702 can affect an ECG reading of thesubject 4702. One solution is to blank the ECG reading duringneurostimulation, for example using the system of FIG. 47Hi. The subject4702 is connected to an ECG system 4704 as usual to measure the rate andrhythm of heartbeats. Sometimes, an ECG amplifier 4708 may be used toamplify signals from the ECG system 4704 prior to providing the sensedinformation on an ECG display 4710. The system shown in FIG. 47Hiincludes an ECG blanker 4706 between the ECG system and the ECGamplifier. The ECG blanker 4706 is configured to capture and manipulatedata from the ECG system 4704 prior to sending such data to the ECGamplifier 4708. The subject 4702 is also connected to a neurostimulationsystem 4712, for example the neurostimulation systems includingelectrode structures and the like as described herein. Otherneurostimulation systems, including for other indications, are alsopossible. In some examples, the neurostimulation system 4712 maycomprise the ECG blanker 4706. The ECG blanker 4706 can inhibit orprevent a neurostimulation waveform and/or effects of neurostimulationon an ECG signal from corrupting an ECG signal.

In some examples, the ECG blanker 4706 can receive a signal from theneurostimulation system 4712 when the neurostimulation system 4712 isapplying neurostimulation. The signal can also open a circuit of the ECGblanker 4706 to interrupt the signal between the ECG system 4704 and theECG amplifier 4708. When the ECG amplifier 4708 does not receive asignal during neurostimulation, the ECG display 4710 may be blank.Stopping sending the signal when not applying neurostimulation canre-close the circuit between the ECG system 4704 and the ECG amplifier4708. In some examples, the neurostimulation system 4712 can send aseparate signal to the ECG blanker 4706 to cause a similar effect. TheECG blanker 4706 may comprise, for example, a blanking circuit, acomparator, a relay, combinations thereof, and the like.

In some examples, the ECG blanker 4706 uses deterministic timing topredict when heartbeats will occur, and instructs the neuromodulationsystem 4712 to not apply neurostimulation during those time windows, forexample so the ECG signal is not blanked when a user would expect to seea heartbeat. During neurostimulation, the signal to the ECG amplifier4708 is blanked (e.g., at least during the biphasic waveform), whichinhibits or prevents high energy stimulation noise from saturating theECG amplifier 4708. The ECG signal may be held at a constant voltageduring stimulation pulses. For complicated heartbeats (e.g., prematureventricular contraction (PVC), bigeminy, etc.), additional blankingand/or other ECG signal manipulation may be used.

FIG. 47Hii schematically illustrates an example method of modifying anECG waveform. During a first duration, R waves of ECGs are detected ormonitored. The R to R interval 4720 (FIG. 41Hii) of the detected ECGsare measured. A weighted sum average of the R to R intervals iscalculated. In some examples, beats well outside the weighted sum may beexcluded, for example because they may be indicative of a PVC, a missedbeat, etc.

The window of time for the next beat can be estimated using the weightedsum average. In startup mode or if a stable R to R interval cannot beestablished, the neurostimulation duty cycle can drop (e.g., to 20%).The prediction window timing can be dynamic based on the heart rate. Forexample, a faster rate may be used for a smaller window and/or a slowerrate may be used for a wider window.

The neurostimulation is blanked from occurring during the estimatedwindow when a heartbeat is expected. In some examples, neurostimulationis applied between an expected T wave and an expected P wave (e.g., asillustrated in FIG. 47Hiii). In some examples, neurostimulation isapplied between an expected T wave and an expected Q wave. In someexamples, neurostimulation is applied between an expected S wave and anexpected Q wave. In some examples, neurostimulation is applied betweenan expected S wave and an expected P wave. Blanking the neurostimulationcan inhibit or prevent blanking of the ECG amplifier input at a timewhen a heartbeat is expected. The rate of neurostimulation may bemodulated slightly to move a stimulation pulse outside of the expectedheartbeat window. Multiple stimulation pulses may be skipped to avoidthe expected heartbeat window.

In some examples, the ECG amplifier 4708 has an input blanking circuitthat is controlled by a neurostimulation signal (e.g., from the ECGblanker 4706 or directly from the neurostimulation system 4712). Duringactive neurostimulation (e.g., having a biphasic waveform), the ECGamplifier 4708 input is blanked. The input potential may be sampled andheld during the blanking. The ECG amplifier 4708 is thereby notdisrupted by the neurostimulation signal.

FIG. 47Hiii schematically illustrates an example ECG waveformuncorrupted by application of neurostimulation. A waveform corrupted bythe application of the neurostimulation (e.g., without blankingneurostimulation) may be unsuitable for use by equipment and/or staff todiagnose issues with the subject, falsely trigger alarms, or cause otherissues. As described above, FIG. 47Hiii shows an example measured R to Rinterval 4720. Using the methods and systems described herein, forexample, neurostimulation is applied between a T wave 4722 and a P wave4724. Stated oppositely, during the duration between the T wave 4722 andthe P wave 4724, neurostimulation is not blanked and is allowed tooccur. Two example biphasic neurostimulation signals are shown in dashedcircles 4726, 4728. For example, if the duration between the T wave 4722and the P wave 4724 is 1 second, the dashed circle 4726, which includestwo cycles, would be about 120 Hz, and the dashed circle 4728, whichincludes four cycles, would be about 240 Hz. These are schematicillustrations and it will be appreciated that the stimulation waves(shape, pulse width, frequency, amplitude, etc.) can vary.

In some examples, because the time to the next R wave is known, a time(e.g., in milliseconds) or a percentage of the R-R interval may be usedto set the blanking periods. For example, if the R-R interval is onesecond, stimulation may be permitted for 300 milliseconds after an Rwave and then blanked after 700 milliseconds after the R wave, about 300milliseconds before the next expected R wave. For another example,stimulation may be permitted for 30% of the R-R interval after an R waveand then blanked after 70% of the R-R interval after the R wave, about30% of the R-R interval before the next expected R wave. These times andpercentages are for example purposes only, and the actual times andpercentages used can be based on statistical analysis, experience,tolerance for stimulation during T waves, tolerance for stimulationduring P waves, duty cycle, effect on contractility, combinationsthereof, and/or other factors.

Neurostimulation may be allowed to occur or not blanked during otherportions of an R to R interval, as described herein (e.g., T to Q, S toQ, S to P, etc.). In some examples, neurostimulation is blanked betweenan expected P wave and an expected T wave, between an expected P waveand an expected S wave, between an expected Q wave and an expected Twave, and/or between an expected Q wave and an expected S wave. In someexamples, neurostimulation at least partially overlapping a P wave or aT wave is permissible.

FIG. 47I schematically illustrates an example system for filtering noisefrom an ECG signal. The system comprises a filter assembly 4732 betweenthe ECG leads 4730 and the ECG system 4704. In some examples, theneurostimulation system 4712 comprises the filter assembly 4732.

FIG. 47J schematically illustrates an example filter assembly 4732. Thefilter assembly 4732 comprises an ECG lead input 4733, an optionalanalog to digital converter 4734, a filter 4735, an optional digital toanalog converter 4736, and an output to ECG 4737. The ECG lead input4733 is configured to accept input from ECG leads (e.g., a 3 lead ECG, a5 lead ECG, a 12 lead ECG, or others). Rather than plugging the ECGleads into an ECG system, the ECG leads 4730 are plugged into the filterassembly 4732. The analog signals from the ECG leads are received by theanalog to digital converter 4734. The analog to digital converter 4734converts the analog signals from the ECG leads into digital signals. Thedigital signals from the analog to digital converter 4734 are receivedby the digital filer 4735. The filter 4735 may comprise a digitalfilter, for example, a notch filter, a low pass filter, a band-stopfilter, a finite impulse response (FIR) filter, a digital signalprocessor, etc. The filter 4735 may be configured to filter the digitalsignal at a certain frequency. The filter 4735 may be adjustable todifferent frequencies. In some examples, the filter assembly 4732 is incommunication with the neuromodulation system 4712, and theneuromodulation system 4712 sets the filter frequency. In some examples,the filter assembly 4732 includes an input for manually orelectronically setting the filter frequency. The filtered digitalsignals from the filter 4735 are received by the digital to analogconverter 4736. The digital to analog converter 4736 converts thefiltered digital signals from the digital filter 4735 into analogsignals. The analog signals from the digital to analog converter 4736are received by the output to ECG 4737. The output to ECG 4737 maycomprise wires mimicking ECG leads. The analog signals from the outputto ECG 4737 are received by the ECG system 4704, which does notdifferentiate between the analog signals directly from the ECG leads andthe analog signals from the output to ECG 4737. In some examples, theanalog to digital converter 4734 and the digital to analog converter4736 may be omitted, and the filter 4735 may comprise an analog filter.In some examples, one piece of hardware may comprise both the analog todigital converter 4734 and the digital to analog converter 4736. In someexamples, additional hardware may be used to modify the signal to bemore amenable to the ECG system 4704.

FIGS. 47Ki-47Kvii schematically illustrate example effects of filteringnoise from an ECG signal. The filter 4735 is a single digital low passfilter and FIGS. 47Ki-47Kvii show the effects of setting the filter 4735at different frequencies, both before and during neurostimulation.Stimulation at a frequency of 20 Hz, for example in accordance with theexamples described herein, is started at the line 4740.

FIGS. 47Ki shows the effects of using a low pass digital filter 4735having a cutoff frequency set at 100 Hz on an ECG signal. Prior tostimulation, the ECG signal is not affected. After stimulation begins,the ECG signal shows significant noise, and the digital filter 4735 hasvery little effect. The 100 Hz filter does clean up noise on the S-Tsegment of the ECG signal. FIG. 47Kii plots the effect of the filter4735 set at 100 Hz across the frequency spectrum. The stimulationfrequency, 20 Hz, causes a large peak at 20 Hz and a smaller peak at 40Hz. The peaks from the ECG leads (e.g., between about 1 Hz and about 10Hz) are also maintained. In some examples, stimulation at greater than100 Hz may have little effect on an ECG signal, for example because anECG system may include a high pass filter set to a frequency less than100 Hz.

FIGS. 47Kiii shows the effects of using a low pass digital filter 4735having a cutoff frequency set at 30 Hz on an ECG signal. Prior tostimulation, the ECG signal is not affected. After stimulation begins,the ECG signal shows some noise, and the digital filter 4735significantly attenuates the noise caused by of the stimulation. Forexample, R-wave peaks are detectable, and the S-T segment is clean(substantially no noise).

FIGS. 47Kiv shows the effects of using a low pass digital filter 4735having a cutoff frequency set at 20 Hz on an ECG signal. Prior tostimulation, the ECG signal is not affected. After stimulation begins,the ECG signal shows some noise, and the digital filter 4735significantly attenuates the noise caused by of the stimulation, morethan at 30 Hz shown in FIG. 47Kiii. As shown below, matching the filterfrequency to the stimulation frequency does not necessarily produce thebest ECG signal noise reduction effect.

FIGS. 47Kv shows the effects of using a low pass digital filter 4735having a cutoff frequency set at 15 Hz on an ECG signal. Prior tostimulation, the ECG signal is not affected. After stimulation begins,the ECG signal shows some noise, and the digital filter 4735significantly attenuates the noise caused by of the stimulation, morethan at 20 Hz shown in FIG. 47Kiv.

FIGS. 47Kvi shows the effects of using a low pass digital filter 4735having a cutoff frequency set at 10 Hz on an ECG signal. Prior tostimulation, the ECG signal is not affected. After stimulation begins,the ECG signal shows very little noise, and the digital filter 4735significantly attenuates the noise caused by of the stimulation, morethan at 15 Hz shown in FIG. 47Kv. Indeed, the ECG signal before andafter stimulation appears the same. FIG. 47Kvii plots the effect of thefilter 4735 set at 10 Hz across the frequency spectrum. Even at thestimulation frequency, 20 Hz, there is no peak. The peaks from the ECGleads (e.g., between about 1 Hz and about 10 Hz, but including somefrequencies up to about 40 Hz) are reduced, but maintained. Withoutbeing bound by any particular theory, it is believed that the filterknee or −3 dB point for a 10 Hz filter is at a point where interferenceis attenuated at the 20 Hz stimulation frequency. If the filter is setat a frequency lower than 10 Hz (e.g., 5 Hz), then the filter may removedata used for the ECG (e.g., between 1 Hz and 10 Hz) with little or nobenefit versus 10 Hz. In some examples, a series of low pass filters ata frequency higher than 10 Hz may achieve a similar effect, for exampleby increasing the slope of the knee, the −3 dB point, and reducing thecutoff frequency.

Filtering noise from an ECG signal, for example as shown in FIG. 47Kvi,can provide one or more advantages. The ECG display can be clean, withsubstantially no stimulation-induced noise, for reading by a user.Arrhythmia detection can be fully functional without false alarms ormissed detection. Pacing artifact detection can operate without falsedetects. For ECG systems including a filter setup, the setup is notchanged but for the filter used.

In some examples, the filter 4735 may comprise a notch filter, forexample set or adjusted to match the stimulation frequency. A notchfilter may provide a similar advantage as a low pass filter and noteffect the ECG signal at higher frequencies. If certain otherfrequencies are known or expected to be affected by the neurostimulation(e.g., a multiple of the stimulation frequency), a plurality of notchfilters at the expected problem frequencies may be used.

FIG. 47L schematically illustrates an example system for matchingneurostimulation frequency to ECG monitoring frequency. The ECG system4704 typically operates at a single frequency (e.g., 50 Hz or 60 Hz,depending on brand, model, etc.). In some neurostimulation systemsdescribed herein, the frequency range may be between about 2 Hz andabout 40 Hz (e.g., about 20 Hz) to obtain a desired effect on leftventricle contractility. The neurostimulation frequency can interferewith the ECG system 4704 (e.g., producing a corrupted ECG signal). Thefrequency matched neurostimulation system 4740 is configured to applyneurostimulation at the same frequency at which the ECG system 4704operates. In some examples, the neurostimulation frequency 4740 iscoupled to the ECG system 4704 and can detect the operating frequency.In some examples, the neurostimulation frequency 4740 comprises afrequency input controllable by a user (e.g., selectable between apredetermined number of frequencies at which ECG systems 4704 operate).The input may comprise the frequency itself, a brand, a model,combinations thereof, and the like. As discussed, the frequency-matchedfrequency may be less than ideal for having the intended therapeuticeffect. Other stimulation parameters may be modified in view of thefrequency. For example, pulse width may be reduced, amplitude may bereduced, duty cycle may be increased, combinations thereof, and/or thelike. In some examples, frequency may be predetermined rather thanoptimized, and then systems and methods described herein may be used tooptimize other stimulation parameters. In some examples, a stimulationwaveform may be modified to provide the same average energy.

The catheter systems disclosed herein can be delivered, deployed,operated, and removed from the body according to any suitable method.FIGS. 48A-48H illustrate an example method for delivering and deployinga catheter system 4800 comprising an expandable structure 4820 includingelectrodes 4824. The catheter system 4800 may be the same or similar tothe catheter system 3700 or other catheter systems disclosed herein. Thecatheter system 4800 may be delivered through a jugular vein to thesuperior vena cava, right atrium, right ventricle, through the pulmonaryvalve, and into the right pulmonary artery.

As shown in FIG. 48A, a syringe 4813 may be used to insert a needle 4814for initially accessing the jugular vein 4815. A guidewire 4816 may thenbe inserted into the jugular vein 4815 through the needle 4814. As shownin FIG. 48B, the needle 4814 may be removed, and an introducer 4830 maybe inserted into the jugular vein 4815 over the guidewire 4816, suchthat the introducer 4830 spans and maintains the opening into thejugular vein 4815. The introducer may comprise, for example, 11 FrenchARROW-FLEX® introducer from Teleflex, Inc. of Westmeath, Ireland,although other introducers may be used. The introducer may comprise aflexible shaft 4831 and a hemostasis valve 4832.

After the introducer 4830 is inserted into the jugular vein 4815, aSwan-Ganz catheter 4840 may be floated to the right pulmonary artery4842, as illustrated in FIG. 48C. The Swan-Ganz catheter 4840 comprisesan inflatable balloon 4841 at its distal end. The Swan-Ganz catheter4842 may be inserted into the introducer 4830 over the guidewire 4816,and, once the balloon 4841 is distal to the introducer 4830, the balloon4841 may be inflated. The inflated balloon 4841 is carried by thenatural blood flow, pulling the distal tip of the Swan-Ganz catheter4840 into the right pulmonary artery 4842. The guidewire 4816 may bedistally advanced through a guidewire lumen of the Swan-Ganz catheter4840 until the distal end of the guidewire 4816 is positioned in theright pulmonary artery 4842. Once the guidewire 4816 is in place, theballoon 4841 may be deflated and the Swan Ganz catheter 4840 can beproximally retracted out of the vasculature. The catheter assembly 4800may include an inflatable balloon at its distal end such that the SwanGanz catheter 4840 and the guidewire 4816 may be omitted.

An introducer sheath 4833 and dilator 4834 can be tracked over theguidewire 4816 to the pulmonary trunk or the right pulmonary artery4842. When the introducer sheath 4833 is in place, the dilator 4834 canbe withdrawn. The catheter system 4800 may be inserted through theintroducer 4830, through the introducer sheath 4833, and tracked overthe guidewire 4816 to the distal end of the introducer sheath 4833. Ifthe expandable structure 4820 is self-expanding the expandable structurecan be in a radially compressed state in the introducer sheath 4833 andin a radially expanded state out of the introducer sheath 4833. Theexpandable structure 4820 may prolapse from the distal end of theintroducer sheath 4833 by distally advancing the expandable structure,proximally retracting the introducer sheath 4833, and/or combinationsthereof. For example, if the distal end of the introducer sheath 4833 isin the pulmonary trunk, the expandable structure 4820 may be distallyadvanced and follow the guidewire 4816 into the right pulmonary artery4842. FIG. 48D shows the expandable structure 4820 in a radiallyexpanded configuration after exiting the distal end of the introducersheath 4833.

The introducer sheath 4833 may be retracted to a position proximal ordistal to the pulmonary valve 4847. If the catheter system 4800 includesa pressure sensor positioned in the right ventricle 4849, the distal endof the introducer sheath 4833 may be retracted to a position proximal tothe pressure sensor, and thus proximal to the pulmonary valve 4847, toexpose the pressure sensor to the right ventricle. The introducer sheath4833 may be retracted to a position distal to the pulmonary artery 4847such that proximal retraction of the expandable member 4820 causes theexpandable member 4820 to be radially compressed by the introducersheath 4833 and an expanded expandable member 4820 cannot cross thepulmonary valve 4847. If the introducer sheath 4833 is splittable, theintroducer 4830 may be retracted from the body entirely and removed fromthe catheter shaft assembly 4806 by splitting along its circumference.

FIGS. 48D-48E show the expandable structure 4820 positioned within theright pulmonary artery 4842. In FIG. 48D, is in a self-expanded stateafter exiting the distal end of the introducer sheath 4833. In FIG. 48E,the expandable structure 4820 is in a further expanded state, forexample due to retraction of an actuation tube. As seen in FIGS.48D-48E, the durometer of the flexible tubing and/or the hinge of thecatheter shaft assembly 4806 can allow a tight bend (approximately 90degrees) as the catheter system 3800 transitions from the pulmonaryartery trunk into the right pulmonary artery 4842. The catheter shaftassembly 4806 may be positioned firmly against the left side of thepulmonary artery trunk. Upon further expansion, for example 2 mm greaterthan the diameter of the right pulmonary artery 4842 in a maximumsystolic state, the expandable structure 4820 is anchored. Theneuromodulation procedure may occur over several days, so maintaining aposition of the expandable structure 4820 by anchoring in the rightpulmonary artery 4842 may provide consistency over the duration of theprocedure.

The introducer 4830 may optionally be fixed relative to the patientduring the procedure to inhibit or prevent inadvertent repositioning ofthe catheter system 4800. FIG. 48F shows an example of a handle 4810 ofa catheter assembly 4800 that has been inserted into an introducer 4830.A silicone sleeve may be placed over the introducer 4830 and sutured toa surface outside the body of the patient and/or directly sutured to thepatient. In some examples, the introducer 4830 is about 65 cm long andthe catheter shaft assembly 4806 is about 100 cm long, leaving about 35cm of neck 4835. After the introducer sheath 4833 is partiallyretracted, for example proximal to the pulmonary valve 4847, the neck4835 may be reduce to about 15 to 20 cm. The introducer valve 4832 mayform a secure connection between the introducer 4830 and the cathetershaft assembly 4806 of catheter system 4800, such that the cathetersystem 4800 is not easily moved relative to the introducer 4830. Asilicone sleeve can optionally be placed over the actuation shaftassembly 4806 along the neck 4835 to maintain the desired spacing. Aninadvertent dislocation of the expandable structure 4820 may be detectedby a measured change in the heart contractility if the electrodes 4824are shifted out of a proper stimulating position.

The electrode array 4829 of the expandable structure 4820 may bepositioned toward the superior and posterior portion of the rightpulmonary artery 4842 for stimulating one or more cardiopulmonarynerves. Fluoroscopy may be used to visualize the positioning of thecatheter system 4800, including the expandable structure 4820, to ensureproper orientation is achieved, especially relating to thecircumferential orientation the electrode array 4829. Fluoroscopy may beperformed with or without contrast agents. FIG. 48G shows a fluoroscopicimage of the catheter system 4800 inserted into right pulmonary artery4842. The electrode array 4829 of expandable structure 4820 is visiblewithout use of a contrast agent. Navigational guidance systems whichincorporate positional sensors on catheters (e.g., NavX™, from St. JudeMedical Inc.) and/or cardiac mapping systems which map theelectrophysiology of the heart surface may be used in conjunction withfluoroscopy or alternatively to fluoroscopy. Mapping performedadditionally to fluoroscopy may be performed prior to or simultaneouslywith fluoroscopy. Pressure sensors or other means may be used to trackpositions of components of the catheter system, which can reduce oreliminate use of fluoroscopy.

FIG. 48H schematically depicts the activation of all of the electrodes4824 on a single spline for stimulating a target nerve 4843, althoughactual stimulation protocols may include as few as two electrodes 4824,include electrodes 4824 on different splines, etc. The target nerve 4843may be a cardiopulmonary nerve. In some examples, two electrodes 4824positioned on either side of the target nerve 4843 may be activated. Insome examples, the target nerve 4843 may be identified after positioningthe expandable structure 4820 by “electrically moving” the cathetersystem 4800, in which the catheter system 4800 and the expandablestructure 4820 are not physically repositioned, but the selection of“active” electrodes 4824 within the electrode array 4829 is shiftedacross the array 4829 or otherwise altered to better capture the targetnerve 4843. The electrode array 4829 may be positioned so that the nerveis positioned between two or more electrodes (e.g., between twoelectrodes, between three electrodes, between four electrodes, etc.).

In some examples, a voltage pre-pulse may be applied to the tissuesurrounding the target nerve 4843 immediately preceding a stimulationpulse. The pre-pulse may pre-polarize the nearby tissue and make iteasier to stimulate the target nerve 4843 while avoiding stimulation ofnearby pain nerves. For example, a stimulation protocol may include asmaller amplitude pulse with a first polarity (e.g., positive or anodicpolarity) configured to pre-polarize the tissue followed immediately oralmost immediately by a larger amplitude pulse of second polarity (e.g.,negative or cathodic) configured to stimulate the target nerve 4843. Thesecond polarity may be the same or opposite the first polarity. Thepre-pulse may be applied by the same or different electrodes 4824 of theelectrode array 4829.

In some examples of use, the active electrodes which are to be usedduring the stimulation procedure are first identified by a fasttitration. During a fast titration, the patient may be sedated to avoidpain so that the electrodes 4824 may be selectively activated at fullpower to determine which electrode or electrodes 4824 best capture thetarget nerve 4843. After the fast titration, the selected activeelectrodes 4824 may be activated with a lower power and increased todetermine the optimal power setting for stimulating the target nerve4843, during which the patient need not be sedated.

The effects of stimulation parameter titration, including, for example,the effects of changes in stimulation amplitude, pulse width, and/orfrequency may be useful to achieve a desired response. Following a shortduration of stimulation (e.g., 1-2 minutes), LV max +dP/dt may decay tobaseline from peak plateau values after approximately 5 minutes. Sinceprogramming stimulation might be based on a trial and error processwhich could be considerably time-consuming, it would be advantageous toautomate the process based on feedback signals (e.g., heart rate and/orcontractility measures). In some examples, automatic stimulationparameter titration is set up once an electrode or electrode combinationthat produces an increase in contractility has been identified. In someexamples, a responsive electrode may have not yet been identified. Anautomated system that cycles through the electrodes as anodes, cathodes,or uncharged may be used to identify responsive electrodes orcombinations based on, for example, contractility and heart signals, forexample as described herein. Once an electrode combination(cathode(s)/anode(s)) has been selected, the stimulation titration maybe set up.

As a first example, stimulation begins at a pre-defined setting such as20 mA amplitude, 4 ms pulse width, and 20 Hz frequency, and a singlestimulation parameter is used to titrate for effect. The titratablestimulation parameter might include, but is not limited to, amplitude,pulse width, or frequency. Heart rate or a threshold for heart rateand/or contractility (or a surrogate measure for contractility such aspressure) is set by the user to titrate for an effect. Absolute changesor relative changes from a baseline level might be used to titrate theeffect. If an increase in contractility is observed with minimal or noincrease in heart rate, a stimulation parameter (e.g., amplitude) isincreased until a side effect or undesirable increase in heart rate isobserved. The stimulation parameter (e.g., amplitude) is then reduceduntil the undesirable heart rate is no longer observed.

As a second example, stimulation begins at a pre-defined setting such as20 mA amplitude, 4 ms pulse width, and 20 Hz frequency, and a pluralityof stimulation parameters are used to titrate for effect. The titratablestimulation parameters might include, but are not limited to, amplitude,pulse width, or frequency. Heart rate or a threshold for heart rateand/or contractility (or a surrogate measure for contractility such aspressure) is set by the user to titrate for an effect. Absolute changesor relative changes from a baseline level might be used to titrate theeffect. If an increase in contractility is observed with minimal or noincrease in heart rate, each of a plurality of stimulation parameter(e.g., amplitude and pulse width) is increased until a side effect orundesirable increase in heart rate is observed. The stimulationparameters (e.g., amplitude and pulse width) are then reduced until theundesirable heart rate is no longer observed.

The frequency of stimulation may be adjusted to increase or maximize thestimulation response and/or to maintain the stimulation response. Forexample, the frequency may be increased (e.g., from 20 Hz to 40 Hz) toincrease cardiac contractility and/or to achieve a cardiac contractilityplateau more quickly. Stimulating a sympathetic nerve at a higherfrequency may result in additional release of neurotransmitter as morestimulation pulses are being delivered to the nerve terminal to signalthe neurotransmitter release responsible for increasing cardiaccontractility. In some examples, increasing the stimulation frequencymay allow for a more efficient way to search for the appropriateelectrode (e.g., cathode) to use for stimulation by reducing the amountof time it takes to identify a stimulation response. This might involvestarting the initial programming session with a higher frequency thanused for the remainder of patient therapy. In some cases, the therapymight use a higher frequency (e.g., 20 Hz) to identify whethercontractility (or other measure) is changing in a favorable direction,and/or might use a lower frequency (e.g., 10 Hz) if the stimulation isused to maintain therapy. The reduction of stimulation frequency mightbe used as a method to maintain stimulation therapy that is moreefficient. In some examples, increasing the stimulation frequency mayallow for a way to increase the magnitude of the contractility response.

A burst mode of stimulation is contemplated in which a burst ofstimulation is delivered at a specific duty cycle. The frequency ofstimulation during the burst mode (intraburst frequency) may be betweenabout 100 Hz and about 800 Hz (e.g., about 100 Hz, about 200 Hz, about300 Hz, about 400 Hz, about 500 Hz, about 600 Hz, about 700 Hz, about800 Hz, ranges between such values, etc.) and/or the frequency of thebursts (inter-burst frequency) may be between about 0.1 Hz and about 20Hz (e.g., about 0.1 Hz, about 0.5 Hz, about 1 Hz, about 2 Hz, about 5Hz, about 10 Hz, about 15 Hz, about 20 Hz, ranges between such values,etc.). The range of parameters in the burst mode of stimulation may beused to mimic physiological activity of cardiac nerves (e.g., cardiacsympathetic nerves).

Duty cycling for stimulation might be set up using an automated system.For example, cycling initially may be set at a particular setting, forexample 5 minutes on and 1 minute off. Duty cycles may be set, but notlimited to be, in the range of 5 seconds to 30 minute increments, or upto 1 hour increments. Similar to stimulation parameter titration, dutycycle may be varied such that stimulation is delivered only whencontractility and heart rate are in the desired range as specified orobserved by a user. It may be advantageous from an efficiency standpoint(e.g., battery longevity, recharge interval) to ramp down stimulation orstop stimulation during a portion of the decay to baseline. In someexamples, the stimulation duty cycle may be pre-specified. For example,stimulation may be stopped for 1 minute then turned on for 1 minute totake advantage of the slow decay of max +dP/dt to baseline and stillmaintain therapeutic effect. In some examples, stimulation duty cyclemay be set for a specific patient based on a feedback signal (e.g., LVmax+dP/dt) and decay of the feedback signal to baseline when stimulationis turned off. Including a duty cycle to the stimulation in whichstimulation is turned on and off periodically can be advantageous, forexample to allow a user to periodically review ECG, which can containstimulation artifacts when stimulation is turned on.

Stimulation parameters may be set to increase (e.g., maximize) a desiredresponse and/or reduce (e.g., minimize) energy delivered and/or anundesirable response. For example, frequency may be used to identifylocations in the pulmonary artery that are proximate to cardiac tissueand that may result in an undesirable response (e.g., arrhythmia) ifstimulated. Stimulation at 2 Hz at a given amplitude and pulse widthmight engage or activate myocardial tissue and result in 2 Hz activationof the atrium (120 beats per minute). An electrode that induces such aresponse might desirably be avoided, or the amplitude and/or pulse widthmight be reduced to avoid activation of the atrium. This effect can beidentified relatively quickly by a user or the device itself. Thisatrial capture test can be used prior to testing each stimulationelectrode or at the beginning of a programming session to test whichelectrodes might be proximate to myocardial tissue. For another example,sensory or pain fibers transmitting undesirable sensations (e.g.,pressure, pain, etc.) may be activated with concurrent activation ofautonomic nerve fibers. The stimulation vector might be altered totighten the stimulation vector and reduce the distance between anode andcathode, and/or to add anodes around the cathode to tighten the field ofstimulation. The stimulation amplitude and/or pulse width may be reducedto avoid activation of unwanted nerve fibers, alone or in conjunction tochanging of the stimulation vector.

Stimulation may be titrated during an initial session or may be used tomonitor therapy and titrate therapy in an acute or chronic setting.Upper and lower limit thresholds for heart rate and contractilitymeasures may be set to ensure stimulation is delivered within thedesired bounds. Upper and lower limits for stimulation parameters may beset such that that those bounds are not exceeded. Stimulation titrationmight be performed periodically or continuously to ensure thatstimulation is continuing to provide the desired effect.

Other measures of contractility and/or therapy effectiveness that mightbe used to titrate, maintain, or test the effect might include LVpressure, derived LV max +dP/dt, right ventricle pressure, derived RVmax +dP/dt, arterial blood pressure, derived mean arterial pressure,muscle sympathetic nerve activity (MSNA), plasma norepinephrine levels,cardiac output (invasive or non-invasive measures), pulmonary arterypressure, mixed venous oxygen saturation, central venous oxygensaturation, myocardial oxygen consumption, pulmonary artery wedgepressure, stellate ganglion nerve activity, or other physiologicalsignals, and/or combinations thereof. Measures of heart rate can includeexternal ECG (e.g., ECG recorded external to the subject such as usingpatch electrodes on skin) and/or internal ECG (e.g., ECG recordedinternal to the subject such as on the stimulation device (e.g.,electrodes on the device) and/or on a remote device).

Preclinical work investigating endovascular stimulation of cardiacsympathetic nerves from the subclavian artery in a swine model showsthat stimulation of left sympathetic nerves can increase cardiaccontractility as the stimulation amplitude is increased. Leftventricular systolic pressures (LVP) have been shown to generallyincrease as stimulation amplitude is increased, particularly up to about30 volts. In contrast, heart rate has been shown to remain relativelyconstant for low stimulation amplitudes, particularly less than about 15volts, but then increase as stimulation amplitude is increased, thenremain relatively constant for higher stimulation amplitudes,particularly greater than about 30 volts.

Electrode selection may be based on systematic titration. For a givenelectrode array, there might be several million combinations orpermutations for electrode selection (e.g., anode or cathode, amplitude,pulse width, frequency, stimulation duration, duty cycle, etc.). A userinterface can help guide a user through a subset of the stimulationparameter space.

FIG. 56A shows a screen of an example user interface 5600. The userinterface 5600 may be shown, for example, on a screen of the computingdevice 5520 described herein. FIG. 56A shows the screen when intitration mode, which can be engaged by clicking the icon 5602 fortitration mode. Icons for other modes include the icon 5604 for newpatient mode (e.g., to initiate a new subject or patient session inputor import data about the subject), the icon 5606 to interrogate thestimulator device, the icon 5608 for monitor mode (e.g., for monitoringvital data for the subject such as ECG, blood pressure, etc.), the icon5610 for new impedance mode (e.g., for monitoring and/or calculatingimpedance data, resistance data, etc.), the icon 5612 for new settingsmode (e.g., for adjusting stimulator settings such as polarity,electrode selection for anode and/or cathode, amplitude, pulse width,duty cycle, ramp on and/or ramp off durations, limits for alarmsettings, etc.), the icon 5614 for pressure sensor mode (e.g., formonitoring, calibrating, resetting, etc. a pressure sensor), the icon5616 for synchronize mode (e.g., for synchronizing time between astimulator (e.g., the stimulation system 5500) and a computing device(e.g., the computing device 5520), the icon 5618 for data mode (e.g.,for logging changes, for accessing stored data, exporting and/or viewinga database, viewing and/or exporting a log of events, etc.), the icon5620 for comment mode (e.g., for inputting comments such as aboutmedicament doses, subject movement, system issues, etc.), the icon 5622for save mode (e.g., for saving information to a disk and/or externalmemory), the icon 5624 for therapy ramp down mode, the icon 5626 forresent mode (e.g., to reset the stimulator), the icon 5628 for emergencyoff mode (e.g., for immediately stopping all stimulation), the icon 5630for program information mode (e.g., for viewing system softwareversions, firmware, hardware, etc.), the icon 5632 for lab mode (e.g.,for viewing stimulator settings, administrator level settings, etc.),and the icon 5634 for close mode (e.g., to close out of the userinterface 5600). The screen can include a number of icons as describedherein, but more, fewer, and/or alternative icons, functions, modes,sequences, etc. are possible. FIG. 56A shows optional information suchas the connection icon 5636 (e.g., indicating a universal serial bus(USB) connection between the computing device and the stimulationsystem). In some examples, the user interface is configured to store apicture or series of pictures (e.g., fluoroscopic, cine, x-ray, etc.) ofan electrode matrix in the subject. Such data may provide a user withinformation about which electrodes to start testing. A script containinga series of programming steps might be created or modified based atleast partially thereon. In certain such examples, a user may be able tobegin titration using a step or test including a particular combinationof electrodes.

In titration mode as shown in FIG. 56A, the screen may show a schematic5638 of an electrode matrix, for example a 4×5 matrix of 20 electrodes.In some examples, the stimulation system can automatically supply theelectrode matrix schematic 5638. In some examples, the electrode matrixschematic 5638 may be manually created. In some examples, the electrodesbeing used for a test or step may change color, include indicia (e.g.,“anode,” “cathode,” “A” (e.g., as shown in FIG. 56A), “V” (e.g., asshown in FIG. 56A), “+,” “−,” etc.). The screen may optionally showgraphs 5640 (e.g., electrocardiogram, right ventricular pressure,pulmonary artery pressure, left ventricle contractility (e.g.,correlated from a measurement in the right ventricle), heart rate)and/or real-time parameters 5642 (e.g., right ventricular pulsepressure, left ventricle contractility (e.g., correlated from ameasurement in the right ventricle), heart rate, active electrodesimpedance) about the subject. The user interface 5600 may providecontrols for selection and modification of graphs 5640 and/or parameters5642. The screen may optionally show parameters 5644 of a test or stepbeing run at that time (e.g., pulse amplitude, pulse width, frequency,duration, etc.).

Still in titration mode in FIG. 56A, the screen shows a dropdown box5650 that may include a variety of programs. In FIG. 56A, the program“Amplitude test” has been selected. The settings icon 5652 may be usedto adjust parameters for the program, to create a new program, to deleteprograms (e.g., with proper authorization), etc. The icon 5654 can beused to run a selected program. The icon 5654 can be used to stoprunning a selected program. The icon 5654 may include, for example, anoctagonal red button with or without “STOP” indicia. The icon 5658 canbe used to bring up the screen 5680, described in further detail herein.The icon 5660 can be used to reset the program (e.g., after movement ofthe subject, once per day, etc.). The icon 5662 shows which step or testof the program would be run if the icon 5666 was clicked. The icons5664, 5668 can be used to select other steps or tests of the selectedprogram (e.g., the icon 5664 reversing one step or test, the icon 5668advancing one step or test). As noted, the icon 5666 can be clicked torun the step or test shown in the icon 5662. In some examples, after thetest or step is run, the user interface 5600 may automatically advanceto the next step or test. In some examples, after the test or step isrun, the user interface 5600 remains on that step or test until the userchanges the step or test using the icons 5664, 5668. In some example,the user may be forced to decide whether the test was acceptable orunacceptable by using the icons 5670, 5672 before being allowed to use adifferent test.

FIG. 56B shows another screen 5680 of the example user interface 5600 ofFIG. 56A. If the icon 5658 (FIG. 56A) is pressed, the screen 5680 canopen. The screen 5680 includes a table with rows of steps or tests. Theicon 5662 shows that there are 8 steps or tests in the “Amplitude test”program. If needed, a scroll bar can be provided if more steps areincluded than can be viewed on the screen 5600. The first columnprovides the step or test number, from 1 to 8. The second columnprovides the pulse amplitude for that test or step. The third columnprovides the pulse width for that test or step. The fourth columnprovides the frequency for that test or step. The fifth column providesthe duration for that test or step. The sixth column provides theelectrode(s) used as anodes for that test or step. The seventh columnprovides the electrode(s) used as cathode(s) for that test or step. Forexample, referring to the schematic 5638 in FIG. 56A, in Row 1, theelectrode 20 or E20 in the lower right is used as a cathode and theelectrode 15 or E15 immediately above the electrode 20 or E20 is used asthe anode.

The screen 5680 may provide information about the results of the test orstep, if the test or step has been run. For example, the eighth columnprovides the heart rate, the ninth column provides the impedance, thetenth column provides the response, and the eleventh column provides thechange in pressure. Showing more, fewer, alternative, or no results isalso possible. In some examples, the rows may change colors based onuser input, for example to red or green, for example to indicate if anelectrode combination is likely to cause side effects and/or result in atherapeutic response, respectively.

Referring again to FIG. 56A, the icon 5670 may be pressed to indicatethat the user does not like or does not approve of the results of thattest or step. Conversely, the icon 5672 may be pressed to indicate thatthe user likes or approves of the results of that test or step. The usercan input reasons for the approval or disapproval. For example, adropdown box 5674 may be auto-populated with reasons (e.g., regardingside effects, therapeutic effect, etc.). For another example, the usercan manually input comments in the box 5676. To add the comment(s), theuser may click the icon 5678.

Predefined scripts may be used to define stimulation parameters (e.g.,anode or cathode, amplitude, pulse width, frequency, stimulationduration, duty cycle, etc.) that could be used to test which electrodeis providing a therapeutic effect. A user could start with the first setof parameters, then the next, until a suitable location for therapy isfound. In some examples, a user enters a comment indicating whether theelectrode and parameter combination was therapeutic, whether theelectrode and parameter combination elicited a mild side effect, whetherthe electrode and parameter combination elicited a severe side effect,and/or whether the electrode and parameter combination should not betested again (e.g., automatically selected based on indication of asevere side effect, lack of therapeutic response, or other parameter, orby being manually selected). The electrodes or cathode could be markedwith a particular color to identify which electrodes might betherapeutic and which other electrodes may cause unwanted side effects.Once a first set of parameters is evaluated, the user can manually stepthrough the various steps in the script (e.g., set(s) of stimulationparameters) to continue testing the various electrodes in the array. Inthis fashion, the user does not have to set the electrodes andparameters to assess the entire space covered by the electrode array.Instead, a script guides the user through the test stimulation processto identify which electrodes might be most beneficial for therapeuticuse. The program may cycle through the steps automatically, or the usermight indicate that the electrode combination tested was acceptable orunacceptable and that the next step of the script can be evaluated. Theoutput may, for example, comprise a log of some or all of the parameterstested and/or a color coded electrode array that indicates whichelectrodes might be useful for therapy and which electrodes arepreferably avoided. Based on the output, electrodes and stimulationparameters for therapy might be suggested.

In Therapy Ramp Down mode 5624, stimulation may be titrated down to apre-specified level (e.g., from a high stimulation amplitude to a lowstimulation amplitude) so that stimulation is not abruptly stopped. Thehigh stimulation amplitude may be the therapeutic amplitude and the lowstimulation amplitude may be set to 0 V or 0 mA, or a thresholdamplitude (e.g., the amplitude at which the desired response wasstarting to be observed using a feedback signal). In some examples, thefeedback signal may comprise left ventricle max +dP/dt, and the lowamplitude may be set at a level where this signal just started toincrease from its baseline level. A timer may be set to trigger thetherapy ramp down for a specific duration after initiating therapeuticstimulation, such as 30 minutes, 1 hour, 24 hours, 3 days, etc. invarying increments within a time frame in the range of 30 minutes to 5days. The timer to start the therapy ramp down may be set to start whenstimulation starts and/or may be initiated manually at any given time.The countdown to triggering the therapy ramp down may be displayed inthe monitor mode 5608 and/or an alert message may be provided to theuser indicating that the therapy ramp down mode will be initiating soonor is initiating. The target amplitude for the therapy ramp down may beset at the threshold amplitude or at another desired level. Other targetvalues may be included. For example, the slow ramp down of stimulationtherapy may involve a decrease in amplitude, pulse width, rate, and/orduty cycle. In some examples, the duration of the therapy ramp down maybe set at 30 minutes, 1 hour, 24 hours, 3 days or 7 days, or variousdurations within this range.

The electrodes 4824 may be activated in a monopolar or bipolar (e.g.,guarded bipolar) fashion. Monopolar stimulation may use negative orpositive polarity and includes the use of a return conductor. The returnconductor may be at least 5 mm away from the electrodes. For example,the return conductor may be attached to or integrated with a portion ofthe catheter system 4800 or another catheter configured to be in theright ventricle 4849. For another example, the return conductor may beattached to or integrated with a portion of the catheter system 4800 oranother catheter configured to be in the superior vena cava. For yetanother example, the return conductor may be attached to or integratedwith a portion of the catheter system 4800 or another catheterconfigured to be in the brachiocephalic or innominate vein. The currentvector from the electrodes 4824 to the brachiocephalic vein may be awayfrom at least one of the heart and the trachea, which may reduce sideeffects and/or increase patient tolerance. In certain such examples, thejugular vein assessed may be the left jugular vein. The return conductormay comprise a patch affixed to the skin.

Upon completion of the procedure, the catheter system 4800 may beremoved from the body according to any suitable method. The actuationmechanism of the handle 4810 of the catheter system 4800 can be releasedso that the expandable structure 4820 can be in a self-expanded, but notfurther expanded, state. The expandable structure 4820 may then enterthe introducer sheath 4833 by proximal retraction of the expandablemember, distal advancement of the introducer sheath 4833, or acombination thereof. The introducer sheath 4833 may be retracted fromthe body with the catheter system 4800 in tow. The expandable structure4820 may be retracted from the body through the introducer sheath 4833,and then the introducer sheath 4833 may be retracted.

The effectiveness of the neural stimulation on heart contractility,particularly of the left ventricle, can be monitored, for example, bymeasuring pressure within the heart. Pressure may be measured by apressure sensor such as a fluid-filled column, a MEMS sensor, or anothersuitable type of pressure sensor. The pressure sensor may be attached toor integrated with the catheter system 4800, for example, along thecatheter shaft assembly 4806. If the pressure sensor is attached to orintegrated with the catheter system 4800, the sensor may be positionedin the right ventricle. The pressure in the right ventricle may becorrelated to the pressure in the left ventricle, such that the leftventricular pressure and therefore left ventricle contractility may besufficiently approximated. A pressure sensor may alternatively beinserted into the heart through another catheter, and may be placed inthe right ventricle, in the left ventricle, or another suitablelocation. The left ventricular pressure may be used to optimize theeffect of the neural stimulation on heart contractility over the courseof the procedure. The heart contractility may be measurably increased,for example, by 5-12% during the procedure. A single catheter maycomprise a plurality of sensors. For example, one sensor may beconfigured as above and a second sensor may be configured to reside inthe right pulmonary artery. The sensor in the right pulmonary arterycould provide a wedge pressure, which is a reading known to users from aSwan Ganz catheterization procedure. A sensor in the right pulmonaryartery may be usable for safety. For example, if a pressure sensor inthe right pulmonary artery migrated below the pulmonary valve, thenstimulation could be shut off (e.g., immediately upon detection based ona change in pressure (e.g., percentage change or absolute change) and/oran absolute value of pressure (e.g., above or below a certain pressure))in order to inhibit or prevent cardiac arrhythmias.

FIG. 49A is a perspective view of an example expandable structure 4900in an expanded state. Operation of an actuation mechanism, for exampleas described herein, can cause the expandable structure 4900 to expandand contract. The expandable structure 4900 comprises a proximal portion4901 and a distal portion 4903. The expandable structure 4900 comprisesa plurality of splines 4908 and a plurality of inflatable elements 4904a, 4904 b. The splines 4908 may be similar to the splines 3622 of theexpandable structure 3620 or any variants thereof, for example asdescribed herein. The coupling of the splines 4908 at the proximalportion 4901 and/or the distal portion 4903 may be similar to thecoupling of the splines 3622 of the expandable structure 3620 or anyvariants thereof, for example as described herein with respect to FIGS.37G-37J. The expandable structure 4908 may lack or be free of or have nosplines 4908 in the circumferential area of the inflatable elements 4904a, 4904 b. The expandable structure 4900 may be used in an over-the wiresystem or as part of a Swan-Ganz system.

The inflatable elements 4904 a, 4904 b could include, for example,balloons 4904 a 1, 4904 a 2, 4904 b 1, 4904 b 2 that are inflatable viaa single common inflation lumen (e.g., in fluid communication with eachof the balloons 4904 a 1, 4904 a 2, 4904 b 1, 4904 b 2, which couldadvantageously provide uniform inflation), multiple common inflationlumens (e.g., a first inflation lumen in fluid communication with theballoons 4904 a 1, 4904 a 2 and a second inflation lumen in fluidcommunication with the balloons 4904 b 1, 4904 b 2, which couldadvantageously provide uniform inflation of balloons on one side of theexpandable structure), or individual inflation lumens, which couldadvantageously provide full control over inflation of individualballoons. The individual balloons could be compliant and/ornon-compliant. The inflatable elements 4904 a, 4904 b can advantageouslyprovide compliance when navigating the expandable structure 4900 througha catheter. For example, balloons, when deflated, are very soft and cannavigate sharp bends. When inflated, balloons can become rigid and canexpand to appose sidewalls of a large diameter vessel.

The plurality of inflatable elements 4904 a, 4904 b of the expandablestructure 4900 include a first inflatable element 4904 a and a secondinflatable element 4904 b. The inflatable elements 4904 a, 4904 b arecircumferentially opposite or spaced by about 180°. Othercircumferential spacing is also possible (e.g., about 30°, about 45°,about 60°, about 75°, about 90°, about 115°, about 130°, about 145°,about 160°, about 175°, ranges between such values, etc.).Circumferential spacing may be measured, for example between midpoints,between like edges, and other methods as may be appropriate for theconstruction of the inflatable elements. The inflatable element 4904 aincludes a first balloon 4904 a 1 and a second balloon 4904 a 2. Thefirst balloon 4904 a 1 is generally parallel to the second balloon 4904a 2. The inflatable element 4904 b includes a first balloon 4904 b 1 anda second balloon 4904 b 2. The first balloon 4904 b 1 is generallyparallel to the second balloon 4904 b 2. The inflatable elements 4904 a,4904 b could include fewer balloons (e.g., one balloon) or moreballoons. Additionally and/or alternatively to being parallel, theballoons could be longitudinally aligned, angled, circumferential,combinations thereof, and the like. The inflatable elements 4904 a, 4904b may be coupled to proximal and distal hubs. Inflation lumens mayextend through a proximal hub. The inflatable elements 4904 a, 4904 bmay be quilted or subdivided into smaller chambers to control the shapeand/or profile when inflated. For example, opposite sides may be weldedtogether to create chambers or balloons. The subdivided chambers maybetter conform to a vessel wall than a monolithic inflatable element.

The inflatable elements 4904 a, 4904 b may be filled with saline,contrast, or other biocompatible fluids. If the inflatable elements 4904a, 4904 b are filled with contrast, the position and rotationalorientation of the expandable structure 4900 may be viewed underfluoroscopy. If the position and/or rotational orientation of theexpandable structure 4900 is viewed as not desirable, the expandablestructure 4900 may be contracted (e.g., including deflating theinflatable elements 4904 a, 4904 b) and repositioned. If preciserotational orientation is desired, the inflatable elements 4904 a, 4904b may be asymmetrical.

The inflatable elements 4904 a, 4904 b may comprise electrodes 4906 a.The electrodes 4906 a may, for example, be printed on the balloons 4904a 1, 4904 a 2, 4904 b 1, and/or 4904 b 2. In FIG. 49A, only theelectrodes 4906 a on the balloon 4904 a 2 are visible. Some of theballoons 4904 a 1, 4904 a 2, 4904 b 1, 4904 b 2 may include electrodes4906 a and some of the balloons 4904 a 1, 4904 a 2, 4904 b 1, 4904 b 2may lack electrodes 4906 a. For example, the balloons 4904 a 1, 4904 a 2of the inflatable element 4904 a may comprise electrodes 4906 a, and theballoons 4904 b 1, 4904 b 2 of the inflatable element 4904 b may have noelectrodes 4906 a. Conductors for the electrodes 4906 a may be printedon the inflatable elements 4904 a, 4904 b, embedded in material of theinflatable elements 4904 a, 4904 b, and/or extend through inflationlumens. A non-limiting example printing process is described withrespect to FIGS. 23Ni-23Nvix, in which the substrate 2301 could be thematerial of the inflatable elements 4904 a, 4904 b. The electrodes 4906a shown in FIG. 49A are longitudinally spaced along the balloon 4904 a2, but other arrangements are also possible. Additionally oralternatively to being positioned on a balloon, the electrodes 4906 acould be positioned between balloons of the inflatable elements 4904 a,4904 b. Such arrangement could space the electrodes 4906 a from a vesselwall and allow blood to flow past the electrodes 4906 a, for exampleproviding advantages described with respect to FIG. 23L.

The splines 4908 may comprise electrodes 4906 b as described herein, forexample but not limited to as described with respect to the splines 3622of the expandable structure 3620. FIG. 49A illustrates an expandablestructure 4900 in which the inflatable elements 4904 a and/or 4904 bcomprise electrodes 4906 a and the splines 4908 comprise electrodes 4906b. FIG. 49Ai is a perspective view of an example expandable structure4903 in an expanded state. The splines 4908 of the expandable structure4903 do not include any electrodes. All of the electrodes 4906 a of theexpandable structure 4903 are on the inflatable elements 4904 a and/or4904 b. FIG. 49Aii is a perspective view of an example expandablestructure 4905 in an expanded state. The inflatable elements 4904 a,4904 b of the expandable structure 4903 do not include any electrodes.All of the electrodes 4906 b of the expandable structure 4905 are on thesplines 4908. All of the splines 4908 of the expandable structure 4900of FIG. 49A include electrodes 4906 b. Some of the splines 4908 mayinclude electrodes 4906 b and some of the splines 4908 may lackelectrodes 4906 b, regardless of whether the inflatable elements 4904 a,4904 b comprise electrodes. For example, the splines 4908 of theexpandable structure 4905 that include electrodes 4906 b arecircumferentially between a first edge 4912 of the inflatable member4904 a and a second edge 4913 of the inflatable member 4904 b. Forexample, the splines 4908 closest to the inflatable member 4904 a mayinclude electrodes 4906 b while the splines 4908 closest to theinflatable member 4904 b may lack electrodes 4906 b.

The electrodes 4906 a and/or 4906 b can form an electrode matrix. Thenumber of electrodes in the electrode matrix, electrode sizing,electrode spacing, etc. may be in accordance with other systemsdescribed herein. Upon expansion of the expandable structure 4900, 4903,4905, the electrodes of the electrode matrix may be selectivelyactivated for testing nerve capture, calibration, and/or therapy, forexample as described herein.

FIG. 49B is a perspective view of an example expandable structure 4920in an expanded state. The expandable structure 4920 comprises a proximalportion 4921 and a distal portion 4923. The expandable structure 4920includes a plurality of inflatable elements 4924 a, 4924 b. Theinflatable elements 4924 a, 4924 b may be coupled to a catheter 4930 ata proximal end (e.g., to a distal portion or a distal end of thecatheter 4930). The inflatable elements 4924 a, 4924 b may be coupled toa tubular member 4928 at a distal end. The expandable structure 4920 maylack or be free of or have no splines in the circumferential area of theinflatable elements 4924 a, 4924 b. The tubular member 4928 may extendat least partially in a lumen of the catheter 4930. A distal portion ofthe tubular member 4928 may extend laterally out of a side the catheter4930. The tubular member 4928 optionally comprises a lumen, for examplea guidewire lumen. The tubular member 4928 optionally comprises anatraumatic distal tip or nose, for example as shown in the distalportion 4923. The tubular member 4928 may be used to pull the distal tipproximally, which can arc electrodes 4926 a against a vessel wall. Thecatheter shaft 4930 may be used to provide some rigidity to hold theelectrodes 4926 a in place and against the vessel wall. The expandablestructure 4920 may be used in an over-the wire system or as part of aSwan-Ganz system.

The inflatable elements 4924 a, 4924 b could include, for example,balloons 4924 a 1, 4924 a 2, 4924 b 1, 4924 b 2 that are inflatable viaa single common inflation lumen (e.g., in fluid communication with eachof the balloons 4924 a 1, 4924 a 2, 4924 b 1, 4924 b 2, which couldadvantageously provide uniform inflation), multiple common inflationlumens (e.g., a first inflation lumen in fluid communication with theballoons 4924 a 1, 4924 a 2 and a second inflation lumen in fluidcommunication with the balloons 4924 b 1, 4924 b 2, which couldadvantageously provide uniform inflation of balloons in onecircumferential area of the expandable structure), or individualinflation lumens, which could advantageously provide full control overinflation of individual balloons. The inflatable elements 4924 a, 4924 bcan advantageously provide compliance when navigating the expandablestructure 4920 through a catheter.

The plurality of inflatable elements 4924 a, 4924 b of the expandablestructure 4920 include a first inflatable element 4924 a and a secondinflatable element 4924 b. The inflatable elements 4924 a, 4924 b arecircumferentially adjacent or spaced by less than about 30°. Othercircumferential spacing is also possible (e.g., less than about 90°,about 60°, about 45°, about 15°, about 10°, about 5°, ranges betweensuch values, etc.). Circumferential spacing may be measured, for examplebetween midpoints, between like edges, and other methods as may beappropriate for the construction of the inflatable elements. Theinflatable element 4924 a includes a first balloon 4924 a 1 and a secondballoon 4924 a 2. The first balloon 4924 a 1 is generally parallel tothe second balloon 4924 a 2. The inflatable element 4924 b includes afirst balloon 4924 b 1 and a second balloon 4904 b 2. The first balloon4924 b 1 is generally parallel to the second balloon 4924 b 2. Theinflatable elements 4924 a, 4924 b could include fewer balloons (e.g.,one balloon) or more balloons. Additionally and/or alternatively tobeing parallel, the balloons could be longitudinally aligned, angled,circumferential, combinations thereof, and the like. In some examples, asingle inflatable element may include each of the balloons of the device(e.g., each of the balloons 4924 a 1, 4924 a 2, 4924 b 1, 4924 b 2). Aplurality of inflatable elements can provide better wall apposition,compliance, blood flow to the vessel wall, and/or other advantages.

The inflatable elements 4924 a, 4924 b may be filled with saline,contrast, or other biocompatible fluids. If the inflatable elements 4924a, 4924 b are filled with contrast, the position and rotationalorientation of the expandable structure 4920 may be viewed underfluoroscopy. If the position and/or rotational orientation of theexpandable structure 4920 is viewed as not desirable, the expandablestructure 4920 may be contracted (e.g., including deflating theinflatable elements 4924 a, 4924 b) and repositioned.

The inflatable elements 4924 a, 4944 b may comprise electrodes 4926 a.The electrodes 4926 a may, for example, be printed on the balloons 4924a 1, 4924 a 2, 4924 b 1, and/or 4924 b 2. Some of the balloons 4924 a 1,4924 a 2, 4924 b 1, 4924 b 2 may include electrodes 4926 a and some ofthe balloons 4924 a 1, 4924 a 2, 4924 b 1, 4924 b 2 may lack electrodes4926 a. For example, the balloons 4924 a 1, 4924 b 2 of the inflatableelement 4924 a may comprise electrodes 4926 a, and the balloons 4924 b1, 4924 b 2 of the inflatable element 4924 b may have no electrodes 4926a. For another example, one of the balloons 4924 a 1, 4924 a 2 of theinflatable element 4924 a may comprise electrodes 4926 a, and one of theballoons 4924 b 1, 4924 b 2 of the inflatable element 4924 b maycomprise electrodes 4926 a. Conductors for the electrodes 4926 a may beprinted on the inflatable elements 4924 a, 4924 b, embedded in materialof the inflatable elements 4924 a, 4924 b, and/or extend throughinflation lumens. A non-limiting example printing process is describedwith respect to FIGS. 23Ni-23Nvix, in which the substrate 2301 could bethe material of the inflatable elements 4924 a, 4924 b. The electrodes4926 a shown in FIG. 49B are longitudinally spaced along the balloon4924 a 2, but other arrangements are also possible. Additionally oralternatively to being positioned on a balloon, the electrodes 4926 acould be positioned between balloons of the inflatable elements 4924 a,4924 b. Such arrangement could space the electrodes 4926 a from a vesselwall and allow blood to flow past the electrodes 4926 a, for exampleproviding advantages described with respect to FIGS. 23L and 53B.

The tubular member 4928 may comprise electrodes 4926 b, for examplesimilar to splines as described herein. FIG. 49B illustrates anexpandable structure 4920 in which the inflatable elements 4924 a and/or4924 b comprise electrodes 4924 a and the tubular member 4928 compriseelectrodes 4926 b, but in some examples only the inflatable elements4924 a, 4924 b comprise electrodes 4926 a or only the tubular member4928 comprises electrodes 4926 b.

The electrodes 4926 a and/or 4926 b can form an electrode matrix. Thenumber of electrodes in the electrode matrix, electrode sizing,electrode spacing, etc. may be in accordance with other systemsdescribed herein. Upon expansion of the expandable structure 4920, theelectrodes of the electrode matrix may be selectively activated fortesting nerve capture, calibration, and/or therapy, for example asdescribed herein.

The expandable structure 4920 may be expanded in vasculature atorientations similar to those described with respect to the expandablestructure 4120. For example, the vasculature may include a pulmonarytrunk, a right pulmonary artery (e.g., as illustrated in FIG. 41G), anda left pulmonary artery. In some examples, the catheter 4930 isasymmetric such that the catheter shaft can bend (e.g., during floatingin a Swan-Ganz system) to naturally align the expandable structure 4920with the right pulmonary artery.

FIG. 49C is a perspective view of an example expandable structure 4940in an expanded state. The expandable structure 4940 comprises a proximalportion 4941 and a distal portion 4943. The expandable structure 4940includes a plurality of inflatable elements 4944 a, 4944 b, 4944 c, 4944d (not visible in the view of FIG. 49C). The inflatable elements 4944 a,4944 b, 4944 c, 4944 d may be coupled to a catheter 4950 at a proximalend. The inflatable elements 4944 a, 4944 b, 4944 c, 4944 d may becoupled to the catheter 4950 at a distal end. The inflatable elements4944 a, 4944 b, 4944 c, 4944 d may be coupled to the catheter 4950between the proximal and distal ends (e.g., continuously ordiscontinuously). The catheter 4950 optionally comprises a lumen, forexample a guidewire lumen. The expandable structure 4940 may be used inan over-the wire system or as part of a Swan-Ganz system.

The inflatable elements 4944 a, 4944 b, 4944 c, 4944 d could eachinclude, for example, one or more balloons that are inflatable via asingle common inflation lumen (e.g., in fluid communication with each ofthe balloons, which could advantageously provide uniform inflation),multiple common inflation lumens (e.g., a first inflation lumen in fluidcommunication with the balloons of the inflatable elements 4944 a, 4944c and a second inflation lumen in fluid communication with the balloonsof the inflatable elements 4944 b, 4944 d, which could advantageouslyprovide uniform inflation of balloons in select opposing circumferentialareas of the expandable structure), or individual inflation lumens,which could advantageously provide full control over inflation ofindividual balloons. One or more of the inflatable elements 4944 a, 4944b, 4944 c, 4944 d may comprise a plurality of balloons, for example asdescribed herein with respect to FIGS. 49A-49B. The inflatable elements4944 a, 4944 b, 4944 c, 4944 d can advantageously provide compliancewhen navigating the expandable structure 4940 through a catheter.

The plurality of inflatable elements 4944 a, 4944 b, 4944 c, 4944 d ofthe expandable structure 4940 include a first inflatable element 4944 a,a second inflatable element 4944 b, a third inflatable element 4944 c,and a fourth inflatable element 4944 d. Other numbers of inflatableelements are also possible (e.g., 2, 3, 5, 6, 7, 8, 9, 10, etc.). FIG.49Ci is a perspective view of an example expandable structure 4943 in anexpanded state. The expandable structure 4943 comprises six inflatableelements 4944 a, 4944 b, 4944 c, 4944 d (not visible), 4944 e (notvisible), 4944 f. The inflatable elements 4944 a, 4944 b, 4944 c, 4944 dmay be uniformly circumferentially spaced. For example, circumferentialspacing may be about 30°, about 36° (e.g., for 10 inflatable elements) ,about 40° (e.g., for 9 inflatable elements), about 45° (e.g., for 8inflatable elements), about 51° (e.g., for 7 inflatable elements), about60° (e.g., for 6 inflatable elements), about 72° (e.g., for 5 inflatableelements), about 75°, about 90° (e.g., for 4 inflatable elements), about115°, about 120° (e.g., for 3 inflatable elements), about 130°, about145°, about 160°, about 180° (e.g., for 2 inflatable elements), rangesbetween such values, etc.). The inflatable elements 4944 a, 4944 b, 4944c, 4944 d may be non-uniformly circumferentially spaced. The inflatableelements 4944 a, 4944 b, 4944 c, 4944 d may be circumferentiallyclustered (e.g., the inflatable elements 4944 a, 4944 b, 4944 c on oneside of a longitudinal axis and the inflatable element 4944 c on theopposite side of the longitudinal axis). In some examples, the clusteredinflatable elements may comprise electrodes 4946 a and the opposinginflatable element may lack electrodes. Circumferential spacing may bemeasured, for example between midpoints, between like edges, and othermethods as may be appropriate for the construction of the inflatableelements.

The inflatable elements 4944 a, 4944 b, 4944 c, 4944 d may be filledwith saline, contrast, or other biocompatible fluids. If the inflatableelements 4944 a, 4944 b, 4944 c, 4944 d are filled with contrast, theposition and rotational orientation of the expandable structure 4940 maybe viewed under fluoroscopy. If the position and/or rotationalorientation of the expandable structure 4940 is viewed as not desirable,the expandable structure 4940 may be contracted (e.g., includingdeflating the inflatable elements 4944 a, 4944 b, 4944 c, 4944 d) andrepositioned. If precise rotational orientation is desired, theinflatable elements 4944 a, 4944 b, 4944 c, 4944 d may be asymmetrical.

The inflatable elements 4944 a, 4944 b, 4944 c, 4944 d may compriseelectrodes 4946 a. The electrodes 4946 a may, for example, be printed onone or more of the balloons of the inflatable elements 4944 a, 4944 b,4944 c, 4944 d. Some of the balloons may include electrodes 4946 a andsome of the balloons may lack electrodes 4946 a. For example, theballoons of the inflatable elements 4944 a, 4944 b may compriseelectrodes 4946 a, and the balloons of the inflatable element 4944 c,4944 d may have no electrodes 4946 a. Conductors for the electrodes 4946a may be printed on the inflatable elements 4944 a, 4944 b, 4944 c, 4944d, embedded in material of the inflatable elements 4944 a, 4944 b, 4944c, 4944 d, and/or extend through inflation lumens. A non-limitingexample printing process is described with respect to FIGS. 23Ni-23Nvix,in which the substrate 2301 could be the material of the inflatableelements 4944 a, 4944 b, 4944 c, 4944 d. The electrodes 4946 a of theexpandable structure 4940 are longitudinally spaced along the balloon4944 a 2, but other arrangements are also possible. For example, FIG.49Cii is a perspective view of an example expandable structure 4945 inan expanded state in which the expandable structure 4945 comprises tworows of electrodes 4946 a, 4946 b on each of the balloons of theinflatable elements 4944 a, 4944 b.

The electrodes 4946 a and/or 4946 b can form an electrode matrix. Thenumber of electrodes in the electrode matrix, electrode sizing,electrode spacing, etc. may be in accordance with other systemsdescribed herein. Upon expansion of the expandable structure 4940, 4943,4945, the electrodes of the electrode matrix may be selectivelyactivated for testing nerve capture, calibration, and/or therapy, forexample as described herein.

Referring again to FIG. 49Ci, each of the inflatable elements 4944a-4944 f comprises a lumen 4952. The lumens 4952 can provide a greatercross-sectional area for blood flow, for example compared to closedinflatable elements. The lumens 4952 may also allow the expandablestructure 4943 to be more compactible, for example compared to closedinflatable elements. In some examples, the inflatable elements 4944a-4944 f may comprise resilient or self-expanding material. In certainsuch examples, inflation media, lumens, etc. may be omitted. Theelectrodes 4946 a, 4946 b are not shown in FIG. 49Ci for simplicity. Thelumens 4952 may, for example, be thin balloon members that can reduce(e.g., minimize) occlusion of the blood vessel, but provide sufficientradial expansion to contact a vessel wall.

FIG. 49D is a perspective view of an example expandable structure 4960in an expanded state. The expandable structure 4960 comprises a proximalportion 4961 and a distal portion 4962. The expandable structure 4960comprises a first spine 4968 a, a second spine 4968 b, and a pluralityof splines 4964 extending between the first spine 4968 a and the secondspine 4968 b. In a collapsed state, the first spine 4968 a may beproximally retracted compared to the expanded state. In the collapsedstate of some examples, the first spine 4968 a and the second spine 4968b may be longitudinally aligned. In the collapsed state of someexamples, a distal portion of the first spine 4968 a and a proximalportion of the second spine 4968 b may longitudinally overlap. Theexpandable structure 4960 may comprise shape-memory material such asnitinol that transforms from the collapsed state to the expanded stateupon release of a force (e.g., confinement in a catheter) and/or achange in temperature. The expandable structure may be expandable bydistally advancing the first spine 4968 a relative to the second spine4968 b and/or by proximally retracting the second spine 4968 n relativeto the first spine 4968 a. In some examples, the expandable structure4960 may comprise shape-memory material to expand to a first expandedstate and may be further expanded to a second expanded state by distallyadvancing the first spine 4968 a relative to the second spine 4968 band/or by proximally retracting the second spine 4968 n relative to thefirst spine 4968 a. This further expansion can help to anchor theexpandable structure in a vessel, for example as described herein withrespect to FIGS. 37Li-37Liv. In some examples, the spines 4968 a, 4968 band the splines 4964 may be cut from a single hypotube to form amonolithic support structure. In some examples, some or all of thespines 4968 a, 4968 b and the splines 4964 may be formed independentlyand then coupled.

The splines 4964 of the expandable structure 4960 are in pairs that arelongitudinally spaced along each of the spines 4968 a, 4968 b. Otherconfigurations are also possible. For example, single splines 4964 couldbe longitudinally spaced along each of the spines 4968 a, 4968 b. Foranother example, single splines 4964 could longitudinally overlap (e.g.,but not circumferentially overlap). For yet another example, more thantwo splines 4964 could extend between the spines 4968 a, 4968 b.

The splines 4964 may comprise electrodes 4966 as described herein, forexample but not limited to as described with respect to the splines 3622of the expandable structure 3620. In the expandable structure 4960 ofFIG. 49D, one spline 4964 of each of the pairs of splines 4964 compriseselectrodes 4966 and the other spline 4964 of the pairs of splines doesnot comprise electrodes 4966. The splines 4964 comprising electrodes4966 are on one side of a first plane comprising a longitudinal axis ofthe expandable structure 4960 and the splines 4964 not comprisingelectrodes 4966 are on an opposite side of the first plane. Theelectrodes 4966 are on portions of the splines 4964 that on one side ofa second plane comprising the longitudinal axis and the portions of thesplines 4964 on an opposite side of the second plane do not compriseelectrodes 4966. Such an arrangement can help to target a portion of avessel or a nerve location and/or reduce profile in the contractedstate. The spines 4968 a, 4869 b can be pulled into a catheter (e.g.,being deployed and/or retract). The splines 4964 can increase (e.g.,optimize) electrode placement on a vessel wall. One or both of thespines 4968 a, 4869 b can increase (e.g., optimize) contact of thesplines 4964 and the electrodes 4966 against a vessel wall.

FIG. 50A is a perspective view of an example expandable structure 5000in an expanded state. The expandable structure 5000 comprises a proximalportion 5001 and a distal portion 5002. The expandable structure 5000comprises a plurality of splines 5004 between the proximal and distalends. The splines 5004 radially converge in the proximal portion 5001.The proximal portion 5001 may be considered closed. A closed proximalend can make retraction of the expandable structure 5000 into a cathetermore reliable that expandable structures having an open proximal end.The splines 5004 are radially outward in the distal portion 5002. Someor all of the splines 5004 may comprise electrodes as described herein,for example but not limited to as described with respect to the splines3622 of the expandable structure 3620. For example, threecircumferentially-adjacent splines 5004 may comprise electrodes, and theremaining splines 5004 may be free from electrodes. In some examples,the splines 5004 comprising electrodes are on one side of a planecomprising a longitudinal axis of the expandable structure 5000 and thesplines 5004 not comprising electrodes may be on an opposite side of theplane. The expandable structure 5000 may include additional splines5008, for example distal to the splines 5004 (e.g., as shown in FIG.50A). Additional splines 5008 can help to anchor the expandablestructure 5000 in a vessel.

FIG. 50B is a perspective view of an example expandable structure 5020in an expanded state. The expandable structure 5020 comprises a proximalportion 5021 and a distal portion 5022. The expandable structure 5020comprises a plurality of splines 5024 between the proximal and distalends. The splines 5024 are radially outward in the proximal portion5021. The proximal portion 5021 may be considered open. The proximalportion 5021 of the expandable structure 5020 may comprise proximaltethers, for example as described herein, which can allow for retractionof the expandable structure 5020 into a catheter. The splines 5024 areradially outward in the distal portion 5022. The distal portion 5022 maybe considered open. One open end or two open ends can reduce occlusionand/or enhance blood flow through a vessel in which the expandablestructure 5020 is positioned. Some or all of the splines 5024 maycomprise electrodes as described herein, for example but not limited toas described with respect to the splines 3622 of the expandablestructure 3620. For example, three circumferentially-adjacent splines5024 may comprise electrodes, and the remaining splines 5024 may be freefrom electrodes. In some examples, the splines 5024 comprisingelectrodes may be on one side of a plane comprising a longitudinal axisof the expandable structure 5020 and the splines 5024 not comprisingelectrodes are on an opposite side of the plane. The expandablestructure 5020 may include additional splines 5028, for example proximaland distal to the splines 5024 (e.g., as shown in FIG. 50B). Additionalsplines 5028 can help to anchor the expandable structure 5020 in avessel.

FIG. 50C is a perspective view of an example expandable structure 5040in an expanded state. The expandable structure 5040 comprises a proximalportion 5041 and a distal portion 5042. The expandable structure 5040comprises a plurality of splines 5044, 5045 between the proximal anddistal ends. The splines 5044 are radially outward in the proximalportion 5041. The proximal portion 5041 may be considered open. Theproximal portion 5041 of the expandable structure 5040 may compriseproximal tethers, for example as described herein, which can allow forretraction of the expandable structure 5040 into a catheter. In theexpandable structure 5040, the splines 5044 converge to twocircumferential points 5046. If tethers are attached to the points 5046such that the points 5046 can be retracted into a catheter, the entireexpandable structure 5046 can be collapsed into the catheter. Thesplines 5045 are radially outward in the distal portion 5042. The distalportion 5042 may be considered open. One open end or two open ends canreduce occlusion and/or enhance blood flow through a vessel in which theexpandable structure 5040 is positioned. Some or all of the splines5044, 5045 may comprise electrodes as described herein, for example butnot limited to as described with respect to the splines 3622 of theexpandable structure 3620. For example, three circumferentially-adjacentsplines 5044, 5045 may comprise electrodes, and the remaining splines5044, 5045 may be free from electrodes. In some examples, the splines5044, 5045 comprising electrodes may be on one side of a planecomprising a longitudinal axis of the expandable structure 5040 and thesplines 5044, 5045 not comprising electrodes are on an opposite side ofthe plane.

The expandable structures 5000, 5020, 5040 may comprise shape-memorymaterial such as nitinol that transforms from a collapsed state to theexpanded state upon release of a force (e.g., confinement in a catheter)and/or a change in temperature. In some examples, the splines 5004,5024, 5044, 5045 and optionally the additional splines 5008, 5028 may becut from a single hypotube to form a monolithic support structure. Insome examples, some or all of the splines 5004, 5024, 5044, 5045 andoptionally the additional splines 5008, 5028 may be formed independentlyand then coupled.

FIG. 51A is a perspective view of an example expandable structure 5100in an expanded state. The expandable structure 5100 comprises a proximalportion 5101 and a distal portion 5102. The expandable structure 5100comprises a plurality of splines 5104 between the proximal and distalends. The splines 5104 are radially outward in the proximal portion5101. The proximal portion 5101 may be considered open. In theexpandable structure 5100, the splines 5104 converge to twocircumferential points 5105. Tethers 5110 are attached to the points5105, which can allow for retraction of the expandable structure 5100into a catheter, for as described herein with respect to FIGS.51Ei-51Ev. The tethers 5110 may comprise, for example, structural cord,wire, urethane tubing, etc. In some examples, electrical connectors forthe electrodes 5106 may be bundled to form the tethers 5110. The splines5104 are radially outward in the distal portion 5102. The distal portion5102 may be considered open. One open end or two open ends can reduceocclusion and/or enhance blood flow through a vessel in which theexpandable structure 5100 is positioned. The tethers 5110 can reduce(e.g., minimize) cardiac motion. The tethers 5110 can provide strainrelief from the catheter. If the tethers 5110 are considered as astring, then motion of a catheter cannot push the expandable structure5100. If slack is left in place, the tethers 5110 cannot pull, whichcould allow a catheter body to migrate (e.g., from a pulmonary artery tothe right ventricle) or even removed altogether. If the catheter body isin place, for example in a right ventricle, then cardiac motion shouldnot push or pull on the expandable structure 5100, which decouplescardiac motion.

Some or all of the splines 5104 may comprise electrodes 5106 asdescribed herein, for example but not limited to as described withrespect to the splines 3622 of the expandable structure 3620. Forexample, in the expandable structure 5100 illustrated in FIG. 51A, fourcircumferentially-adjacent splines 5104 comprise electrodes 5106, andthe remaining splines 5104 are free from electrodes 5106. In someexamples, such as the expandable structure 5100, the splines 5104comprising electrodes 5106 are on one side of a plane comprising alongitudinal axis of the expandable structure 5100 and the splines 5104not comprising electrodes 5106 are on an opposite side of the plane. Theexpandable structure 5100 may include additional splines 5108, forexample distal to the splines 5104 (e.g., as shown in FIG. 51A).Additional splines 5108 can help to anchor the expandable structure 5100in a vessel.

The electrodes 5106 can form an electrode matrix. The number ofelectrodes in the electrode matrix, electrode sizing, electrode spacing,etc. may be in accordance with other systems described herein. Uponexpansion of the expandable structure 5100, the electrodes 5106 of theelectrode matrix may be selectively activated for testing nerve capture,calibration, and/or therapy, for example as described herein. Theelectrodes 5106 of the expandable structure 5100 are capable of beingpositioned at the pulmonary artery notch or bifurcation between the leftpulmonary artery and the right pulmonary artery. The additional splines5108 can anchor the expandable structure 5100 in a vessel (e.g., rightpulmonary artery). For example, additional splines 5108 that are thedistal-most part of the expandable structure 5100 can extend into aright pulmonary artery, for example distal to the pulmonary arterybifurcation. The electrodes 5106 can be cantilevered back toward thepulmonary artery bifurcation.

FIG. 51B is a perspective view of an example expandable structure 5120in a collapsed state. FIG. 51C is a perspective view of the exampleexpandable structure 5120 in an expanded state. The expandable structure5120 may include similar features to the expandable structure 5100(e.g., splines 5124, additional splines 5128, cut pattern, materials,etc.) with a few differences. For example, the expandable structure 5120may comprise tethers 5110, but any such tethers 5110 are omitted fromFIGS. 51B and 51C for simplicity. For another example, the electrodes5106 of the expandable structures are on tubular elements for eachspline 5104, but the electrodes 5126 are individually coupled to thestruts 5124. As shown in FIG. 51B, in the collapsed state, theelectrodes 5126 are able to nest. Nested electrodes 5126 may providereduced delivery profile. The electrodes of other expandable structuresdescribed herein may also be configured to nest in a collapsed state.

FIG. 51D is a cross-sectional view of an example catheter 5140 forcontaining an expandable structure in a collapsed state. The catheter5140 schematically shows how a 9 Fr outer diameter catheter can containcontaining 1 mm electrodes on four splines 5144 (e.g., the electrodes5106 on the splines 5104, the electrodes 5126 on the splines 5124) and aguidewire lumen 5142 configured to allow passage of a 0.025″ guidewire.Portions of expandable structures not comprising electrodes tend to becontained more easily and are not shown.

FIGS. 51Ei-51Ev illustrate an example method of retrieving an expandablestructure 5160. The expandable structure 5160 only includes two struts5164 comprising electrodes for simplicity, but the expandable structure5160 may include similar features to, for example, the expandablestructures 5100, 5120. The expandable structure 5160 comprises tethers5162 coupled to proximal points. FIGS. 51Ei-51Ev also show a sheath 5170of a catheter that may be used to capture the expandable structure 5160.The catheter optionally comprises a tubular member 5172. The tubularmember 5172 may comprise a guidewire lumen. In some examples, thetethers 5172 are coupled to the tubular member 5172 (e.g., as shown inFIG. 51Ei). In certain such examples, the tubular member 5172 may belongitudinally moved relative to the sheath 5170 for expansion and/orcapture of the expandable structure 5170. In some examples, the tethers5172 are coupled to a different tubular member. In some examples, thetethers 5172 are not coupled to a tubular member, for example extendingproximal to the proximal end of the sheath 5170 for direct manipulationby a user. The tubular member 5172 optionally comprises a tip 5174. Thetip 5174 may comprise an atraumatic distal end. The tip 5174 may beconfigured to occlude the sheath 5170, for example as shown in FIG.51Ev.

FIG. 51Ei shows the expandable structure 5160 in an expanded state afterrelease from the sheath 5170. In a vessel, the struts 5164 would apposethe vessel walls and the electrodes 5166 would form an electrode matrixconfigured to stimulate a target nerve. FIG. 51Eii shows the expandablestructure 5160 after the tubular member 5172 is proximally retractedand/or the sheath 5170 is distally advanced. The proximal ends of thetethers 5162 are proximate to the distal end of the sheath 5170, and theexpandable structure is still in the expanded state. FIG. 5 lEiii showsthe expandable structure 5160 after the tubular member 5172 is furtherproximally retracted and/or the sheath 5170 is further distallyadvanced. The tethers 5162 are in the sheath 5170, and the proximalportion of the expandable structure 5160 is in the sheath 5170. Thetethers 5162 guide the proximal portion of the expandable structure 5160radially inward and into the distal end of the sheath 5170. The proximalportion of the expandable structure 5160 is radially compressed by thesheath 5170, radially compressing the remainder of the expandablestructure 5160 towards the compressed state. FIG. 51Eiv shows theexpandable structure 5160 after the tubular member 5172 is furtherproximally retracted and/or the sheath 5170 is further distallyadvanced. Much of the expandable structure 5160 is in the sheath 5170.FIG. 51Ev does not show the expandable structure 5160 because, after thetubular member 5172 is further proximally retracted and/or the sheath5170 is further distally advanced, the expandable structure 5160 is inthe sheath 5170 in the collapsed state. The tip 5174 mates with thedistal end of the sheath 5170. The expandable structure 5170 may beconfigured to collapse into the sheath 5170 upon failure and/ormovement, for example as described herein.

FIG. 51Fi is a perspective view of an example expandable structure 5180in an expanded state. FIG. 51Fii is a side view of the exampleexpandable structure 5180 of FIG. 51Fi. The expandable structure 5180 iscoupled to a guidewire sheath 5182. The expandable structure 5180 can betracked over a guidewire 5183 by positioning a proximal end of theguidewire 5183 in a lumen of the guidewire sheath 5182. The expandablestructure 5180 comprises a first plurality of splines 5184 between theproximal and distal ends. From proximal to distal, the first pluralityof splines 5184 extend from one side of a hub 5186 longitudinally andcircumferentially towards the distal end. Such a configuration can, forexample, reduce an amount of spline material in a lumen such as a bloodvessel. The extension from the hub 5186 can allow for retraction of theexpandable structure 5180 into a catheter 5181 (e.g., by proximallyretracting the guidewire sheath 5182 and/or distally advancing thecatheter 5181). The expandable structure may include a second pluralityof splines 5188. As best seen in FIG. 51Fii, the second plurality ofsplines 5188 can form an annular cage configured to anchor theexpandable stricture 5180 in a vessel (e.g., a right pulmonary artery).For example, the splines 5188 that are the distal-most part of theexpandable structure 5180 can extend into a right pulmonary artery, forexample distal to the pulmonary artery bifurcation. In an expandedstate, the guidewire sheath 5182 is proximate to a circumference of theexpandable structure 5180, for example as opposed to being in a centralportion of the expandable structure 5180. A guidewire sheath 5182proximate a circumference can reduce an amount of material in a centralpart of a lumen such as a blood vessel. This can reduce interaction ofthe guidewire sheath 5182 with blood, reducing risk of embolization. Theguidewire sheath 5182 may include a coating to inhibitendothelialization if the guidewire sheath 5182 is adjacent to a vesselwall for an extended period of time.

Some or all of the splines 5184 may comprise electrodes 5186 asdescribed herein. In some examples, an electrode structure (e.g., asdescribed with respect to FIG. 53A) may be coupled to the splines 5184before coupling the splines 5184 to the hub 5186. In the expandablestructure 5180 illustrated in FIG. 51Fi, four circumferentially-adjacentsplines 5184 can comprise electrodes, and the two remaining splines 5184may be free from electrodes 5186. As best seen in FIG. 51Fii, thesplines 5184 comprising electrodes may be on one side of a planedividing the expandable structure 5180 and the splines 5184 notcomprising electrodes may be on an opposite side of the plane. Theelectrodes can form an electrode matrix. The number of electrodes in theelectrode matrix, electrode sizing, electrode spacing, etc. may be inaccordance with other systems described herein. Upon expansion of theexpandable structure 5180, the electrodes of the electrode matrix may beselectively activated for testing nerve capture, calibration, and/ortherapy, for example as described herein. The electrodes of theexpandable structure 5180 are capable of being positioned, for example,in a right pulmonary artery.

FIG. 52Ai is a perspective view of an example expandable structure 5200in an expanded state. FIG. 52Aii is a side view of the expandablestructure 5200 of FIG. 52Ai in an expanded state. FIG. 52Aiii is an endview of the expandable structure 5200 of FIG. 52Ai in an expanded state.The expandable structure 5200 comprises a proximal portion 5201 and adistal portion 5202. The expandable structure 5200 comprises a pluralityof splines 5204 between the proximal and distal ends. In a fullyexpanded state, the splines 5204 protrude radially outward in theproximal portion 5201 to form almost a spherical shape. In theexpandable structure 5200, the splines 5204 converge to acircumferential point, optionally coupled to a proximal hub 5205, whichcan allow for retraction of the expandable structure 5200 into acatheter 5209, for as described herein with respect to FIGS. 22F, 22M,36B, 37B, and 50A. The splines 5204 are pliable, which can help thesplines 5204 to conform ti the shape of a vessel in which they arepositioned (e.g., a right pulmonary artery). The expandable structure5200 may include additional splines 5208, for example distal to thesplines 5204 (e.g., as shown in FIG. 52A). Additional splines 5208 canhelp to anchor the expandable structure 5200 in a vessel. For example,certain expandable structures may only include highly compliant splines,which may be acceptable for short-term use, but anchoring splines 5208can help to maintain the positions of compliant splines over a longtreatment duration (e.g., 0.5-6 days). The additional splines 5208 inthe distal portion 5202 may be substantially circumferentiallypositioned about and/or parallel to a longitudinal axis of theexpandable structure 5200. The distal portion 5202 may be consideredopen. One open end or two open ends can reduce occlusion and/or enhanceblood flow through a vessel in which the expandable structure 5200 ispositioned.

In some examples, the proximal portion 5201 comprises a first set ofsplines 5204 and the distal portion 5202 comprises a second set ofsplines 5208. The first set of splines 5204 may have a higher compliance(e.g., lower spring rate) than the second set of splines 5208. In someexamples, in a fully expanded state, the proximal portion 5201 has afirst shape (e.g., spherical) and the distal portion 5202 has a secondshape (e.g., cylindrical). In some examples, in a fully expanded state,the proximal portion 5201 has a first diameter and the distal portion5202 has a second diameter less than the first diameter. For example,with reference to FIG. 52Aiii, a difference in radius Δr between thesplines 5204 of the proximal portion 5201 and the splines 5208 of thedistal portion 5202 may be about 1 mm to about 4 mm (e.g., about 1 mm,about, 2 mm, about 3 mm, about 4 mm, ranges between such values, and thelike). In a partially expanded state (e.g., limited by a vessel wall),the first diameter and the second diameter may be the same.

In some examples, the proximal portion 5201 and the distal portion 5202may be monolithically cut from single tube or sheet, which can reduce aneed to couple the proximal portion 5201 and the distal portion 5202. Acoupling point can be a point of weakness prone to fracture. In someexamples, the proximal portion 5201 may be cut from a first tube orsheet and the distal portion 5202 may be cut from a second tube or sheetdifferent than the first tube or sheet, and the proximal portion 5201may be coupled to the distal portion 5202. Cutting from different tubesor sheets can more effectively decouple certain properties such asradial stiffness. In some examples, cutting of a monolithic structurecan attempt to mimic the effects of separate cutting, for example byvarying thickness and/or geometry, twisting, etc.

Some or all of the splines 5204 may comprise electrodes 5206 asdescribed herein, for example but not limited to as described withrespect to the splines 3622 of the expandable structure 3620. Forexample, in the expandable structure 5200 illustrated in FIG. 52Aii, twocircumferentially-adjacent splines 5204 comprise electrodes 5206, andthe remaining splines 5204 are free from electrodes 5206. In someexamples, such as the expandable structure 5200, the splines 5204comprising electrodes 5206 may be on one side of a plane comprising alongitudinal axis of the expandable structure 5200 and the splines 5204not comprising electrodes 5206 may be on an opposite side of the plane.The electrodes 5206 may be overmolded in insulating material, forexample as described with respect to FIGS. 53A-53Eii. The splines 5204may be coupled to a hub 5205 after coupling overmolded electrodestructures.

The electrodes 5206 can form an electrode matrix. The number ofelectrodes in the electrode matrix, electrode sizing, electrode spacing,etc. may be in accordance with other systems described herein. FIG. 52Aiand 52Aii illustrate two splines 5204 each having three electrodes 5206,forming a 2×3 matrix of six electrodes 5206. Upon expansion of theexpandable structure 5200, the electrodes 5206 of the electrode matrixmay be selectively activated for testing nerve capture, calibration,and/or therapy (e.g., neurostimulation to increase left ventriclecontractility), for example as described herein. In some examples, eachof the splines 5204 may include electrodes 5206, forming a fullycircumferential electrode array. A fully circumferential electrode arraycan advantageously avoid rotational repositioning. A partiallycircumferential electrode array (e.g., as illustrated in FIGS. 52Ai and52Aii can reduce cost, device size, and/or manufacturing complexity. Apartially circumferential electrode array can be rotationallyrepositioned as needed. For example, the electrode structure 5200 can bedeployed, tested (e.g., by activating combinations of electrodes), andthen if needed, retrieved, torqued, redeployed, and retested, which canbe repeated as needed.

The electrodes 5206 of the expandable structure 5200 are capable ofbeing positioned at the pulmonary artery notch or bifurcation betweenthe left pulmonary artery and the right pulmonary artery. The additionalsplines 5208 can anchor the expandable structure 5200 in a vessel (e.g.,right pulmonary artery, left pulmonary artery). For example, additionalsplines 5208 that are the distal-most part of the expandable structure5200 can extend into a right pulmonary artery or a left pulmonaryartery, for example distal to the pulmonary artery bifurcation.

FIG. 52Aiv illustrates the expandable structure 5200 of FIG. 52Aipositioned in a right pulmonary artery 5214. The splines 5208 anchor theexpandable structure 5200 in the right pulmonary artery. With referenceto FIG. 2B, in some examples, the splines 5208 are to the right of theright lateral plane 216. The splines 5204 conform to the shape of thepulmonary artery 5214, and may conform to the shape of the pulmonarytrunk 5212 and/or left pulmonary artery 5216 depending on the desiredposition of the expandable structure 5200.

FIG. 52Bi is a perspective view of an example expandable structure 5220in an expanded state. FIG. 52Bii is an end view of the expandablestructure 5220 of FIG. 52Bi in an expanded state. The expandablestructure 5220 may share similar features as the expandable structure5200 (e.g., proximal portion 5221, distal portion 5222, etc.). In theexpandable structure 5220, the proximal portion 5221 comprises two typesof splines 5224 a, 5224 b. The splines 5224 a may be similar to thesplines 5204 of the expandable structure 5200. The splines 5224 b arebifurcated between a proximal end of the proximal portion 5221 and adistal end of the proximal portion 5221. The splines 5224 b becomecircumferentially further apart from the proximal end of the proximalportion 5221 towards the distal end of the proximal portion 5221, andbecome circumferentially further apart from the distal end of theproximal portion 5221 towards the proximal end of the proximal portion5221, being furthest apart in an intermediate part of the proximalportion 5221. The bifurcation of the splines 5224 b can help tostabilize a distance between adjacent splines. In some examples, each ofthe splines 5224 b may comprise electrodes. In some examples, each ofthe splines 5224 a may comprise electrodes. In some examples, some ofthe splines 5224 b may comprise electrodes. In some examples, some ofthe splines 5224 a may comprise electrodes. In some examples, some ofthe splines 5224 b may comprise electrodes and some of the splines 5224a may comprise electrodes. As described herein, more splines 5224 aand/or 5224 b including electrodes can reduce repositioning, whereasfewer splines 5224 a and/or 5224 b including electrodes can reducedevice size, cost, and/or manufacturing complexity.

As best seen in FIG. 52Bii, the splines 5224 a, 5224 b alternate aboutthe circumference of the expandable structure 5220. In some examples,the bifurcated splines 5224 b may be circumferentially adjacent. In someexamples, the expandable structure 5220 can include more bifurcatedsplines 5224 b than splines 5224 a. In some examples, the expandablestructure 5220 can include only bifurcated splines 5224 b and no splines5224 a. In some examples, the expandable structure 5220 can includefewer bifurcated splines 5224 b than splines 5224 a. A difference inradius Δr between the splines 5224 a, 5224 b of the proximal portion5221 and the splines 5228 of the distal portion 5222 may be about 1 mmto about 4 mm (e.g., about 1 mm, about, 2 mm, about 3 mm, about 4 mm,ranges between such values, and the like). The distal portion 5222illustrated in FIG. 52Bi includes six cells each tapering to a proximalpoint and then a tail. Three of the tails are bifurcated splines 5224 band three of the tails are splines 5224 a. In some examples, only one ofthe tails is a bifurcated spline 5224 b.

FIG. 52Ci is a perspective view of an example expandable structure 5230in an expanded state. FIG. 52Cii is a side view of the expandablestructure 5230 of FIG. 52Ci in an expanded state. The expandablestructure 5230 may share similar features as the expandable structure5200 (e.g., proximal portion 5231, distal portion 5232, etc.). In theexpandable structure 5230, the proximal ends of the splines 5234 includeS-shaped features best seen in FIG. 52Cii, and then converge to a point.The splines 5234 have an S-shaped feature at the proximal end beforeconverging to a circumferential point 5235. The S-shaped features can,for example, reduce length of the expandable structure 5230 in the mainpulmonary artery. For example, compared to the expandable structure5200, the expandable structure 5230 can be several millimeters shorterbecause the splines 5234 bend distally then proximally rather thancontinuing distally. The S-shaped structures can provide a radialspring, which can attenuate movement. Attenuated movement can help tomaintain a position of the electrodes 5206 during movement, for exampledue to blood flow and/or respiration. The spring properties of theS-shaped features can be tuned or customized based on, for example,thickness of the splines 5234, geometry of the splines 5234, sliding ahub 5235 along a guidewire sheath 5237, combinations thereof, and thelike. The electrodes 5236 may be positioned on and/or proximate to anapex of the splines 5234.

FIG. 52Ciii illustrates the expandable structure of FIG. 52Ci positionedin a right pulmonary artery. The splines 5238 anchor the expandablestructure 5230 in the right pulmonary artery. With reference to FIG. 2B,in some examples, the splines 5238 are to the right of the right lateralplane 216. The splines 5234 conform to the shape of the pulmonary artery5214, and may conform to the shape of the pulmonary trunk 5212 and/orleft pulmonary artery 5216 depending on the desired position of theexpandable structure 5230.

FIG. 52Di is a perspective view of an example expandable structure 5240in an expanded state. FIG. 52Dii is a side view of the expandable 5240structure of FIG. 52Di in an expanded state. FIG. 52Diii is an end viewof the expandable structure 5240 of FIG. 52Di in an expanded state. Theexpandable structure 5240 may share similar features as the expandablestructure 5230 (e.g., proximal portion 5231 including S-shaped features,distal portion 5232, etc.). In the expandable structure 5240, theproximal portion 5241 comprises splines 5244 that are bifurcated betweena proximal end of the proximal portion 5241 and a distal end of theproximal portion 5241. The splines 5244 become circumferentially furtherapart from the proximal end of the proximal portion 5241 towards thedistal end of the proximal portion 5241, and become circumferentiallyfurther apart from the joint between cells of the distal portion 5242towards the proximal end of the proximal portion 5241, being furthestapart in an intermediate part of the proximal portion 5241. As perhapsbest seen in FIG. 52Diii, pairs of the splines 5244 are side-by-side forat least the S-shaped feature. The bifurcation of the splines 5244 canhelp to stabilize a distance between adjacent splines.

FIG. 52E is a perspective view of an example expandable structure 5250in an expanded and advanced state. The expandable structure 5250comprises a proximal portion 5251 and a distal portion 5252. Like theexpandable structures 5200, 5220, 5230, 5240, for example, the distalportion comprises a plurality of struts 5258 configured to anchor theexpandable structure 5250 in a vessel. The proximal portion 5251comprises a plurality of splines 5255 coupling the distal portion 5252to an elongate member. The proximal portion 5251 also comprises aguidewire sheath 5254 comprising electrodes 5256. A distal end of theguidewire sheath 5254 is fixedly coupled to the distal portion 5252. Aproximal end of the guidewire sheath 5254 is movable relative to theexpandable structure 5250. As the guidewire sheath 5254 is distallyadvanced, the guidewire sheath 5254 bows radially outward. In someexamples, the distal portion 5252 is configured to anchor in a leftpulmonary artery and the guidewire sheath 5254 is configured to bow intoa right pulmonary artery. In some examples, the guidewire sheath 5254 isnot configured to bow, but a spline 5255 comprises electrodes 5256 andis configured to bow. In some examples, the guidewire sheath 5254comprises electrodes 5256 and is configured to bow, and at least onespline 5255 comprises electrodes 5256 and is configured to bow. In someexamples, at least two of the splines 5255 comprise electrodes 5256 andare configured to bow. Deflecting a guidewire sheath 5254 comprisingelectrodes 5256 can reduce the number of components of the expandablestructure 5250. Multiple splines 5255 and/or a guidewire sheath 5254comprising electrodes 5256 can form nested arcs forming an electrodematrix. Multiple splines 5255 and/or a guidewire sheath 5254 comprisingelectrodes 5256 can be independently or dependently operated.

FIGS. 52Fi and 52Fii illustrate an example method of using theexpandable structure 5250 of FIG. 52E. The illustrated anatomy modelcomprises a pulmonary trunk 5212, a right pulmonary artery 5214, andleft pulmonary artery 5216. The distal portion 5252 is anchored in theleft pulmonary artery 5216. In FIG. 52Fi, the proximal end of theguidewire sheath 5254 is distally advanced, as illustrated by the arrow5257, which causes the guidewire sheath 5254 to start to bow into theright pulmonary artery 5214, as indicated by the arrow 5258. In FIG.52Fii, the proximal end of the guidewire sheath 5254 is further distallyadvanced, as illustrated by the arrow 5257, which causes the guidewiresheath 5254 to further bow into the right pulmonary artery 5214, asindicated by the arrow 5258. The position of the guidewire sheath 5254can be fixed (e.g., by fixing the positon of the proximal end of theguidewire sheath 5254), and neurostimulation signals can be applied tothe electrodes 5256.

FIG. 52Gi is a perspective view of an example expandable structure 5260in a collapsed state. In comparison to expandable structures comprisingstent-like features, the expandable structure 5260 can provide asignificantly smaller collapsed state. FIG. 52Gii is a perspective viewof the example expandable structure 5260 of FIG. 52Fii in an expandedstate. The device 5260 comprises a first wire 5262, a guidewire sheath5264, and a second wire 5268 extending distally from a catheter 5265.The guidewire sheath 5264 comprises electrodes 5266 and is configured tobow, for example similar to the guidewire sheath 5254 of the expandablestructure 5450. In comparison to expandable structures comprisingstent-like features, the expandable structure 5260 can provide aone-size-fits-all device. For example, depending on radial strength,stent-like structures may need to have an expanded diameter within acertain percentage of a diameter of a vessel into which it is deployed;if the stent-like structure is too large, the vessel may be damaged orthe expandable structure may only be able to expand to a state that isnot optimal for the procedure (e.g., having electrodes too closetogether); if the stent-like structure is too small, the expandablestructure may not be able to anchor in the vessel such that theelectrodes may move during a procedure. By contrast, the expandablestructure 5260 is not necessarily subject to such potentialdisadvantages because preloaded opposing wires can be adaptable to anydiameters.

FIGS. 52Giii-52Gv illustrate an example method of using the expandablestructure 5260 of FIG. 52Gi. In FIG. 52Giii, the expandable structure5260 has been advanced in the left pulmonary artery 5216. The expandablestructure is expanded such that the first wire 5262 is preloaded againsta first wall of the left pulmonary artery 5216 and the pulmonary trunk5212 and the second wire 5268 is preloaded against the opposite wall ofthe left pulmonary artery 5216. The expandable structure 5260preferentially bends with the anatomy of the left pulmonary artery 5216.In FIG. 52Giv, the expandable structure 5260 is proximally retracted inthe expanded state, as shown by the arrow 5272. The second wire 5268snaps into the ostium of the right pulmonary artery 5214, providing aself-aligning method of accurately deploying the expandable structure5260 into a specific anatomical position. The first wire 5262 and thesecond wire 5268 anchor the expandable structure 5260 in place. In FIG.52Gv, the guidewire sheath 5276 is distally advanced, causing theguidewire sheath 5264 to bow into the right pulmonary artery 5214, asshown by the arrow 5278. The electrodes 5266 on the guidewire sheath5264 can be used to target a nerve, for example as described in detailherein. The guidewire sheath 5264 moves independently from the firstwire 5262 and the second wire 5268, which advantageously decouplesanchoring structure and electrode structure. As shown in FIG. 52Gv, theguidewire sheath 5264 may optionally extend radially outward of thesecond wire 5268. As described with respect to the expandable structure5250, the guidewire sheath 5264 and/or one or more splines may includethe electrodes 5266, and positioning the electrodes 5266 on theguidewire sheath 5264 can reduce the number of components.

FIG. 52Gvi illustrates an example method of using a version of theexpandable structure 5260 comprising an electrode spline 5265. Theelectrode spline 5265 can be operated independently of the guidewiresheath 5264 or with the guidewire sheath 5264. When the electrode spline5265 is in an advanced position, as shown in FIG. 52Gvi, the electodespline 5265 is nested with the guidewire sheath 5264, forming atwo-dimensional or three-dimensional matrix of the electrodes 5266. Theelectrodes 5266 may be positioned on the guidewire sheath 5264 and/orelectrode spline 5265 such that in the advanced position the electrodes5266 are in a position to target a particular anatomy (e.g., a nervethat when stimulated increases left ventricle contractility).

FIG. 53A is a perspective view of an example electrode assembly 5300.The electrode assembly 5300 can be used in the expandable structuresdescribed herein. The electrode assembly 5300 comprises electrodes 5306interspersed between electrically insulating material 5304. Theelectrodes 5306 are each electrically coupled to an electrical connector5307. In examples in which the electrodes 5306 are on a tubular device,the electrical connectors 5307 may extend through a lumen 5310 of thetubular device.

FIG. 53B is a scanning electron microscope image of an electrode 5306area in the circle 53B of FIG. 53A at 3,560× magnification. The surfaceof the electrode 5306 is surface modified by laser ablation. The laserablation creates valleys 5322 and hills 5324. In some examples, thedepth of the valleys 5322 compared to the hills 5324 is between about0.1 mm and about 1 mm (e.g., about 0.1 mm, about 0.2 mm, about 0.3 mm,about 0.5 mm, about 0.7 mm, about 0.9 mm, about 1 mm, ranges betweensuch values, etc.). The laser ablation can be in one direction, twodirections (e.g., a first direction and a second direction transverse(e.g., perpendicular) to the first direction), or more directions. Insome examples, the effective surface area of an electrode 5306 can beincreased by about 300× to about 500× by laser ablation. The electrode5306 is a cylindrical electrode, but laser ablation can be used on anyof the electrodes described herein.

The laser ablation can space portions of the electrode 5306 from thevessel wall, which can allow blood to flow over the electrode 5306.Referring again to FIG. 23F, the insulating material 2316, for example,may act as a spacer. Allowing blood to flow over the electrode 2308 mayinhibit corrosion of the electrode 2308. Allowing blood to flow over theelectrode 2308 may allow blood to contact the vessel wall 2397 in thearea of the electrode 2308 such that cells may be replenished. In someexamples, the electrode may comprise longitudinal channels, a bumpysurface, etc. to allow blood to flow radially outward of the electrode2308 but to still be closer to the nerve 2399. In certain such examples,surface area of the electrode 2308 may be advantageously increased.

FIGS. 53Ci-53Ciii-2 schematically illustrate an example method ofmanufacturing an electrode assembly 5300 a, 5300 b such as the electrodeassembly 5300 of FIG. 53A. FIG. 53Ci illustrates the placement ofelectrodes 5306 in a mold 5340. When forming a cylindrical electrodeassembly 5300, the mold 5340 may have a cylindrical or annular shape.The electrodes 5306 are coupled to electrical connectors 5307. FIG.53Cii-1 illustrates overmolding the electrodes 5306 in the mold 5340with a biocompatible electrically insulating material 5342 such asurethane, silicone, combinations thereof, and the like. The electricalconnectors 5307 are in substantially the same position as in FIG. 53Ci.Some portions of the electrical connectors 5307 are encapsulated in theinsulating material 5342 and other portions of the electrical connectors5307 are not encapsulated in the insulating material 5342, for examplebeing in the lumen 5310 between inner surfaces of the insulatingmaterial 5342. FIG. 53Cii-2 also illustrates overmolding the electrodes5306 in the mold 5340 with a biocompatible electrically insulatingmaterial 5342 such as urethane, silicone, combinations thereof, and thelike. The electrical connectors 5307 are moved, for example by tensionand/or by radially outward force of the overmolding process, such thatsubstantially all of the electrical connectors 5307 are encapsulated inthe insulating material 5342. Encapsulating the electrical connectors5307 in the insulating material 5342 can help to protect the wires,reduce the risk of electrical leakage, and/or reduce the risk of wirecorrosion (e.g., through pinholes in insulation of the electricalconnectors 5307). In some examples, encapsulating the electricalconnectors 5307 in the insulating material 5342 can reduce or eliminateelectrically insulating the individual electrical connectors. FIGS.53Ciii-1 and 53Ciii-2 illustrate removal of the electrode assembly 5300a, 5300 b, respectively, from the mold 5340. The resulting electricalassembly 5300 a, 5300 b is shown as a cross-section along the line53C-53C in FIG. 53A. The overmolding process can be applied tonon-annular electrodes as well.

FIGS. 53Di and 53Dii schematically illustrate another example method ofmanufacturing an example electrode assembly 5300 c such as the electrodeassembly 5300 of FIG. 53A. FIG. 53Di illustrates the placement ofelectrodes 5306 in a mold 5350. When forming a cylindrical electrodeassembly 5300, the mold 5350 may have a cylindrical or annular shape.The mold 5350 includes features 5352 such as annular grooves, which arethe inverse of features overlap features 5354 such as annular ridgesthat are formed during the molding process. The electrodes 5306 arecoupled to electrical connectors 5307. With reference to FIG. 53Cii-1,the electrodes 5306 are overmolded in the mold 5350 with a biocompatibleelectrically insulating material 5342 such as urethane, silicone,combinations thereof, and the like. The electrical connectors 5307 arein substantially the same position as in FIG. 53Cii-2, for example movedby tension and/or by radially outward force of the overmolding process,such that all or substantially all of the electrical connectors 5307 areencapsulated in the insulating material 5342. Encapsulating theelectrical connectors 5307 in the insulating material 5342 can help toprotect the wires, reduce the risk of electrical leakage, and/or reducethe risk of wire corrosion (e.g., through pinholes in insulation of theelectrical connectors 5307). In some examples, encapsulating theelectrical connectors 5307 in the insulating material 5342 can reduce oreliminate electrically insulating the individual electrical connectors.FIG. 53Dii illustrates the electrode assembly 5300 c after removal fromthe mold 5350. The resulting electrical assembly 5300 c is shown as across-section along the line 53C-53C in FIG. 53A. The overlap features5354 seal the ends of the electrodes 5306. The overlap features 5354 atleast partially define the dimensions (e.g., longitudinal width) of theelectrically active areas of the electrodes 5306, which can provide morepredictable and/or uniform stimulation. The overlap features 5354 couldspace the electrodes 5306 from a vessel wall and allow blood to flowpast the electrodes 5306, for example providing advantages describedwith respect to FIG. 23L. The overmolding process can be applied tonon-annular electrodes as well.

FIG. 53Ei schematically illustrates another example electrode assembly5300 d such as the electrode assembly 5300 of FIG. 53A. In contrast tothe electrode assembly 5300 c of FIG. 53Dii, in which the overlapfeatures 5354 return to the outer radii of the electrodes 5306longitudinally outward of the electrodes 5306, the overlap features 5356of the electrode assembly 5300 d extend the same or substantially thesame radial width longitudinally outward of the electrodes 5306.Returning to outer radii of the electrodes 5306 as in FIG. 53Dii canreduce material use. Extending the same or substantially the same radialwidth can reduce mold complexity, increase wall apposition, and/orprovide higher manufacturing tolerances.

FIG. 53Eii schematically illustrates another example electrode assembly5300 e such as the electrode assembly 5300 of FIG. 53A. In contrast tothe electrode assembly 5300 d of FIG. 53Ei, in which the overlapfeatures 5356 are smooth or substantially smooth longitudinally outwardof the electrodes 5306, the overlap features 5358 of the electrodeassembly 5300 e include a textured surface, which can form anchorstructures, for example providing advantages described with respect toFIGS. 12A-12D and/or FIG. 27I (e.g., contacting vascular tissue in sucha way that the movement of the electrodes 5306 at the location wherethey contact the vascular tissue is reduced (e.g., minimized) and/orsome of the tissue may enter spaces between the anchor structures toincrease likelihood of tissue engagement). The anchor structures canhave a variety of shapes including conical, barbless hook, ridges andvalleys, combinations thereof, and the like. Compared to the electrodeassembly 5300 d of FIG. 53Ei, an electrode assembly 5300 e includingoverlap features 5358 including a textured surface can reduce materialuse.

FIG. 53F is an outer perspective view of an example electrode 5366. FIG.53G is an inner perspective view of the example electrode 5366 of FIG.53F. For example as described with respect to several expandablestructures herein, a strut 5362 may be cut (e.g., laser cut) from a tubeor sheet (e.g., comprising shape-memory material such as nitinol). Thestrut 5362 also includes an aperture sized and shaped to receive theelectrode 5366.

Electrically insulating material 5364 is coupled to the laser-cut strut5362. As best seen in FIG. 53F, the electrically insulating material5364 may cover an outside of the strut 5362. In some examples, anoutside of the strut 5362 only includes electrically insulating material5364 around the electrode 5366. As best seen in FIG. 53G, theelectrically insulating material 5364 may cover an inside of the strut5362. In some examples, an inside of the strut 5362 only includeselectrically insulating material 5364 around the electrode 5366. In someexamples, an inside of the strut 5362 includes electrically insulatingmaterial 5364 around the electrode 5366 and proximal to the electrode5366 (e.g., under the conductor 5368). The electrode 5366 is coupled toa conductor 5368. The conductor 5368 may be insulated.

The conductor 5368 may be electrically coupled to the electrode 5366without use of solder, welding, etc. For example, the electrode 5366 canpass through the aperture of the strut 5362 and then be deformed (e.g.,swaged, crimped) on the inside to retain the electrode 5366 to the strut5362, for example as shown in FIG. 53G. In some examples, the strut 5362can include a channel or slot into which the conductor 5368 can beinserted. In some examples, electrically insulating material can beapplied over the deformed electrode 5366 and the conductor 5368 on theinside of the strut 5362, after which the electrode 5366 is only exposedon the outside, as shown in FIG. 53F. In some examples, the strut 5362may comprise a plurality of electrodes 5366 coupled thereto in the samemanner. In some examples, an expandable structure can include aplurality of the struts 5362. Each of the plurality of struts 5362 mayinclude a plurality of electrodes 5366 coupled thereto in the samemanner.

FIG. 54A is a schematic view of a heart with an example catheter system5402 including an expandable structure 5408 deployed in the rightpulmonary artery 5409. The catheter system 5402 comprises a firstpressure sensor 5404 in the pulmonary artery 5410 and a second pressuresensor 5406 in the right ventricle 5412. FIG. 54B is a perspective viewof an example pressure sensor 5420 that can be used for the firstpressure sensor 5404 and/or the second pressure sensor 5406. Thepressure sensor 5420 illustrated in FIG. 54B comprises a 1 Fr MEMS-basedpressure sensor including a wire 5422 extending proximally, for exampleavailable from Millar. The pulmonary valve 5411 is between the pulmonaryartery 5410 and the right ventricle 5412. The first pressure sensor 5404and the second pressure sensor 5406 can be used to detect cathetermovement, for example as described with respect to FIG. 54C.

FIG. 54C is a graph illustrating an example use of pressure sensors formonitoring catheter movement. Data from the first pressure sensor 5404is shown in the top graph 5442. Data from the second pressure sensor5406 is shown in the bottom graph 5444. In some examples, data from thefirst pressure sensor 5404 and the second pressure sensor 5406 may bedisplayed on the same graph. In some examples, data from the firstpressure sensor 5404 and the second pressure sensor 5406 may be notdisplayed to a user and/or may be displayable upon user request, but thesystem may be configured to sound an alarm (e.g., send a message over anetwork) upon sensing movement. The data may be on a beat-by-beat basis,every second, or other intervals as may be appropriate. During a firstduration 5446, the data from the pulmonary artery is in a certain rangeand the data from the right ventricle is in a certain range. During asecond duration 5447, the data from the pulmonary artery is in adifferent range and the data from the right ventricle is still in acertain range. The data from the pulmonary artery is in the certainrange of the right ventricle, which may indicate to a user that thefirst pressure sensor 5404 has migrated from the pulmonary artery 5410,past the pulmonary valve 5411, into the right ventricle 5412. Thismigration may be indicative of migration of the catheter system 5402,including the expandable structure 5408 providing stimulation. Upon suchdetection, an alarm may sound (e.g., a wireless message may be sent),stimulation may automatically shut off, the expandable structure may becollapsed, and/or other events may occur. During the duration 5448, thecatheter system 5402 has been moved so that the first pressure sensor5404 and the second pressure sensor 5406 are in the pulmonary artery5410 and the right ventricle, respectively. Monitoring catheter movementcan alert a user to migration, which may cause adverse events such asmyocardium stimulation, arrhythmia, damage to cardiac structures (e.g.,due to unintended catheter removal), etc.

The catheter system 5302 can additionally or alternatively comprisefirst and second pressure sensors configured to detect catheter movementin other positions. For example, a first pressure sensor could beconfigured to detect pressure in the right ventricle and a secondpressure sensor could be used to detect pressure in the right atrium.For another example, a first pressure sensor could be configured todetect pressure in the right atrium and a second pressure sensor couldbe used to detect pressure in the right inferior vena cava. In someexamples, the first and second pressure sensors are configured to detectpressure in adjacent cavities (e.g., separated by a valve). In someexamples, the first and second pressure sensors can be more remote(e.g., separated by a plurality of valves).

FIGS. 54Di and 54Dii illustrate an example method and system fordetecting movement of a catheter 5452. In FIG. 54Di, the catheter 5452is in an as-delivered configuration. For example as illustrated in FIG.54A but with respect to any of the expandable structures describedherein or otherwise, an expandable structure shown by a dashed X isanchored in the right pulmonary artery 5409. Anchoring or positioning isalso or alternatively possible in the left pulmonary artery and/or thepulmonary trunk 5410. The catheter 5452 includes an elongate elementextending from the expandable structure, through the pulmonary trunk5410, through the pulmonary valve 5411, through the right ventricle5412, through the tricuspid valve 5413, through the right atrium 5414,through the vena cava, and out of the subject (e.g., through a carotidvein or a femoral vein). The catheter 5452 includes a first pressuresensor 5454 in the right ventricle 5412. The catheter 5452 optionallyincludes a second pressure sensor 5456 in the pulmonary trunk 5410. Asingle sensor configuration is described in further detail herein. Forexample as described with respect to FIGS. 54A and 54B, the pressuresensors 5454, 5456 may comprise Millar sensors or other types ofpressure sensors.

In FIG. 54Dii, the catheter 5452 has been pulled proximally, asindicated by the arrow 5458. The expandable structure remains anchoredin position as slack in the elongate member of the catheter 5452 isinitially reduced. As shown in FIG. 54Dii, this results in the catheter5452 being pulled next to the annulus of the tricuspid valve 5413. Thefirst sensor 5454 remains in the right ventricle 5412 but makes contactwith the leaflets of the tricuspid valve 5413 and chordae tendenae,which causes a change to the sensor signal even prior to reaching theright atrium 5414. If the catheter 5452 is further proximally retracted,the first sensor 5454 is pulled into the right atrium 5414, furtherchanging the sensor signal. If the catheter 5452 is further proximallyretracted, the slack will have been taken up and forces may start to actto dislodge the expandable structure. The method and system describedwith respect to the first sensor 5454 of FIGS. 54Di and 54Dii canprovide early warning or pre-warning of movement of the catheter 5452even before the expandable structure is moved and stimulation may becompromised.

The optional second sensor 5456 remains in the pulmonary trunk 5410. Forexample as described with respect to FIGS. 54A-54C, the second sensor5456 may be used to confirm movement of the catheter 5452 (e.g.,movement due to the expandable structure becoming unanchored such thatthe second sensor 5456 moves through the pulmonary valve 5411).

FIG. 54E illustrates in a single figure an example method and system fordetecting movement of a catheter 5462. The catheter 5462 is shown in anas-delivered configuration in solid lines in the vena cava and thepulmonary trunk 5410 and in dashed lines in the right ventricle 5412 andthe right atrium 5414, and is shown in an as-pulled configuration insolid lines throughout. In contrast to the catheter 5452 of FIGS. 54Diand 54Dii, the catheter 5462 includes one sensor 5464 shown in anas-delivered position 5464 a and an as-pulled position 5464 b. Incontrast to FIG. 54Dii, the catheter 5462 has been pulled such that theas-pulled position 5464 b is in the right atrium 5414. The sensor 5464provides a right atrium pressure signal upon crossing the tricuspidvalve 5413, which is different than a right ventricle pressure signaland a signal indicating contact with leaflets and chordae of thetricuspid valve 5413. The method and system described with respect tothe sensor 5464 of FIG. 54E can provide early warning or pre-warning ofmovement of the catheter 5462 even before the expandable structure ismoved and stimulation may be compromised.

FIG. 55 is a front view of an example stimulation system 5500. Thestimulation system 5500 comprises a housing 5502, a catheter connector5504 including electrical connectors 5506, a display 5508, and an input5510. The housing 5502 can contain stimulation electronics including aswitch matrix for electrode stimulation. In some examples, a minimumoutput of the stimulation matrix is 25 mA, up to 8 ms, and 100 Hz. Otherminimums, maximums, and specified parameters (e.g., number ofpolarities, pulsing mode, amplitude, phase, voltage, duration,inter-pulse interval, duty cycle, dwell time, sequence, waveform, etc.)are also possible. A computing device 5520 (e.g., networked computerterminal, desktop, laptop, tablet, smartphone, smartwatch, etc.) may becommunicatively coupled to the stimulation system 5500 via wired orwireless system. In some examples, a tablet may be connected to thestimulation system 5500 via a USB connection 5522 (e.g., as shown inFIG. 55). The computing device 5520 may include a display providing agraphical user interface configured to set stimulation parameters,present sensor data, view waveforms, store data, etc. The computingdevice 5520 may be networked to other computing devices, networks, theinternet (e.g., via secured, HIPAA-compliant protocol), etc. Referringagain to FIG. 54A, the electrical connectors 5506 may be configured tointerface with electrical connectors from a pressure sensor (e.g., twopressure sensors). The electrical connectors 5506 may be configured tointerface with electrical connectors from ECG leads (e.g., three leadsfrom skin ECG patches). The electrical connectors 5506 may be configuredto interface with electrical connectors from sensors configured toprovide data usable for contractility measurement. The stimulationsystem 5500, the computing device 5520, and/or another computing devicemay be configured to use the data to provide a contractilitymeasurement. The stimulation system 5500 may include additionalelectrical connectors that are not used to connect to current catheters,but that can provide the ability to update the system for futuredevelopments. The stimulation system 5500, the computing device 5520,and/or another computing device may include embedded programs forstimulation and/or sensing. The stimulation system 5500, the computingdevice 5520, and/or another computing device may include safety alarmsconfigured to alert a user at the stimulation system 5500, the computingdevice 5520, and/or another computing device of an alarm event. In someexamples, a third pressure sensor may provide confirmation (e.g.,detecting that the second pressure sensor 5306 moved from the rightventricle 5312 into the right atrium).

Certain procedures described herein may be divided between users at acatheter lab and an intensive care unit or subject's room. Certain suchprocedures may, for example, still be under the direction of a singleentity controlling the procedure(s). A catheter lab may deploy thedevice in a subject. A catheter lab may perform therapy titration (e.g.,determining stimulation parameters for a maximum tolerable contractilityincrease, determining stimulation parameters for a contractilityincrease greater than a minimum value, determining stimulationparameters for a contractility increase less greater than a maximumvalue, determining stimulation parameters for a heart rate increase lessthan a maximum value, etc.). An intensive care unit and/or subject'sroom may apply therapy at pre-established parameters. An intensive careunit and/or subject's room may monitor therapy (e.g., via ECG, BP/MAP,SvO2, change in contractility, change in pressure, heart rate, etc.). Anintensive care unit and/or subject's room may perform initial and/orfollow-up (e.g., as needed) therapy titration (e.g., determiningstimulation parameters for a maximum tolerable contractility increase,determining stimulation parameters for a contractility increase greaterthan a minimum value, determining stimulation parameters for acontractility increase less greater than a maximum value, determiningstimulation parameters for a heart rate increase less than a maximumvalue, etc.). An intensive care unit and/or subject's room may performtherapy ramp down. Some functions may be performed at any location asappropriate. For example, follow-up titration therapy may be performedby a catheter lab, which may be more experienced at establishingstimulation parameters.

Certain systems described herein may include a network interface tointerface to a LAN, WAN, or the Internet through a variety ofconnections including, but not limited to, standard telephone lines, LANor WAN links, broadband connections, wireless connections (e.g.,Bluetooth, WiFi), combinations thereof, and the like. The networkinterface may comprise a built-in network adapter, network interfacecard, wireless network adapter, USB network adapter, modem, or any otherdevice suitable for interfacing with any type of network capable ofcommunication and performing the operations described herein. Ahospital, catheter lab, ICU, etc. may have equipment or systems alsoconnected to the network that can communicate with the systems describedherein. For example, a practitioner may use a wireless tablet computeror smart device to monitor a plurality of subjects at that location, anda signal about a process described herein (e.g., catheter movementdetection, stimulation effect data, alerts from the subject, etc.) maybe received wirelessly. For example, upon catheter movement detection(e.g., using two sensors as described herein, using one sensor asdescribed herein, etc.), the practitioner may receive a text message,instant message, popup message, etc.

The foregoing description and examples has been set forth merely toillustrate the disclosure and are not intended as being limiting. Eachof the disclosed aspects and examples of the present disclosure may beconsidered individually or in combination with other aspects, examples,and variations of the disclosure. In addition, unless otherwisespecified, none of the steps of the methods of the present disclosureare confined to any particular order of performance. Modifications ofthe disclosed examples incorporating the spirit and substance of thedisclosure may occur to persons skilled in the art and suchmodifications are within the scope of the present disclosure.Furthermore, all references cited herein are incorporated by referencein their entirety.

While the methods and devices described herein may be susceptible tovarious modifications and alternative forms, specific examples thereofhave been shown in the drawings and are herein described in detail. Itshould be understood, however, that the invention is not to be limitedto the particular forms or methods disclosed, but, to the contrary, theinvention is to cover all modifications, equivalents, and alternativesfalling within the spirit and scope of the various examples describedand the appended claims. Further, the disclosure herein of anyparticular feature, aspect, method, property, characteristic, quality,attribute, element, or the like in connection with an example can beused in all other examples set forth herein. Any methods disclosedherein need not be performed in the order recited. Depending on theexample, one or more acts, events, or functions of any of thealgorithms, methods, or processes described herein can be performed in adifferent sequence, can be added, merged, or left out altogether (e.g.,not all described acts or events are necessary for the practice of thealgorithm). In some examples, acts or events can be performedconcurrently, e.g., through multi-threaded processing, interruptprocessing, or multiple processors or processor cores or on otherparallel architectures, rather than sequentially. Further, no element,feature, block, or step, or group of elements, features, blocks, orsteps, are necessary or indispensable to each example. Additionally, allpossible combinations, subcombinations, and rearrangements of systems,methods, features, elements, modules, blocks, and so forth are withinthe scope of this disclosure. The use of sequential, or time-orderedlanguage, such as “then,” “next,” “after,” “subsequently,” and the like,unless specifically stated otherwise, or otherwise understood within thecontext as used, is generally intended to facilitate the flow of thetext and is not intended to limit the sequence of operations performed.Thus, some examples may be performed using the sequence of operationsdescribed herein, while other examples may be performed following adifferent sequence of operations.

The various illustrative logical blocks, modules, processes, methods,and algorithms described in connection with the examples disclosedherein can be implemented as electronic hardware, computer software, orcombinations of both. To clearly illustrate this interchangeability ofhardware and software, various illustrative components, blocks, modules,operations, and steps have been described above generally in terms oftheir functionality. Whether such functionality is implemented ashardware or software depends upon the particular application and designconstraints imposed on the overall system. The described functionalitycan be implemented in varying ways for each particular application, butsuch implementation decisions should not be interpreted as causing adeparture from the scope of the disclosure.

The various illustrative logical blocks and modules described inconnection with the examples disclosed herein can be implemented orperformed by a machine, such as a general purpose processor, a digitalsignal processor (DSP), an application specific integrated circuit(ASIC), a field programmable gate array (FPGA) or other programmablelogic device, discrete gate or transistor logic, discrete hardwarecomponents, or any combination thereof designed to perform the functionsdescribed herein. A general purpose processor can be a microprocessor,but in the alternative, the processor can be a controller,microcontroller, or state machine, combinations of the same, or thelike. A processor can also be implemented as a combination of computingdevices, e.g., a combination of a DSP and a microprocessor, a pluralityof microprocessors, one or more microprocessors in conjunction with aDSP core, or any other such configuration.

The blocks, operations, or steps of a method, process, or algorithmdescribed in connection with the examples disclosed herein can beembodied directly in hardware, in a software module executed by aprocessor, or in a combination of the two. A software module can residein RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory,registers, hard disk, a removable disk, an optical disc (e.g., CD-ROM orDVD), or any other form of volatile or non-volatile computer-readablestorage medium known in the art. A storage medium can be coupled to theprocessor such that the processor can read information from, and writeinformation to, the storage medium. In the alternative, the storagemedium can be integral to the processor. The processor and the storagemedium can reside in an ASIC. The ASIC can reside in a user terminal. Inthe alternative, the processor and the storage medium can reside asdiscrete components in a user terminal.

Conditional language used herein, such as, among others, “can,” “might,”“may,” “e.g.,” and the like, unless specifically stated otherwise, orotherwise understood within the context as used, is generally intendedto convey that some examples include, while other examples do notinclude, certain features, elements, and/or states. Thus, suchconditional language is not generally intended to imply that features,elements, blocks, and/or states are in any way required for one or moreexamples or that one or more examples necessarily include logic fordeciding, with or without author input or prompting, whether thesefeatures, elements and/or states are included or are to be performed inany particular example.

The methods disclosed herein may include certain actions taken by apractitioner; however, the methods can also include any third-partyinstruction of those actions, either expressly or by implication. Forexample, actions such as “positioning an electrode” include “instructingpositioning of an electrode.”

The ranges disclosed herein also encompass any and all overlap,sub-ranges, and combinations thereof. Language such as “up to,” “atleast,” “greater than,” “less than,” “between,” and the like includesthe number recited. Numbers preceded by a term such as “about” or“approximately” include the recited numbers and should be interpretedbased on the circumstances (e.g., as accurate as reasonably possibleunder the circumstances, for example ±5%, ±10%, ±15%, etc.). Forexample, “about 1 V” includes “1 V.” Phrases preceded by a term such as“substantially” include the recited phrase and should be interpretedbased on the circumstances (e.g., as much as reasonably possible underthe circumstances). For example, “substantially perpendicular” includes“perpendicular.” Unless stated otherwise, all measurements are atstandard conditions including temperature and pressure. The phrase “atleast one of” is intended to require at least one item from thesubsequent listing, not one type of each item from each item in thesubsequent listing. For example, “at least one of A, B, and C” caninclude A, B, C, A and B, A and C, B and C, or A, B, and C.

What is claimed is:
 1. A method of detecting catheter movement, themethod comprising: positioning a first sensor in a first body cavity;monitoring a first parameter profile of the first body cavity;positioning a second sensor in a second body cavity; monitoring a secondparameter profile of the second body cavity, the second parameterprofile different than the first parameter profile at a first time; andwhen the second parameter profile is the same as the first parameterprofile at a second time after the first time, taking a cathetermovement action.